Composition and Methods for Stimulating Gastrointestinal Motility

ABSTRACT

The present invention relates to a method of treating a transient impairment of the motility of the gastrointestinal system resulting from postoperative ileus in a patient wherein said method includes the step of administering a therapeutically effective amount of a peptidyl analog of ghrelin to said patient.

This application is a divisional application of pending U.S. Ser. No.16/168,870, filed Oct. 24, 2018, which is a divisional application ofU.S. Ser. No. 15/333,240, filed Oct. 25, 2016, which is a continuationapplication of U.S. Ser. No. 14/628,379, filed Feb. 23, 2015, whichissued as U.S. Pat. No. 9,499,599 on Nov. 22, 2016, which is acontinuation application of U.S. Ser. No. 13/046,324, filed Mar. 11,2011, which issued as U.S. Pat. No. 8,981,054 on Mar. 17, 2015, which isa continuation application of U.S. Ser. No. 11/992,780, filed Mar. 29,2008, which issued as U.S. Pat. No. 7,932,231 on Apr. 26, 2011, which isa United States national filing under 35 U.S.C. § 371 of international(PCT) application No. PCT/US2006/38027, filed Sep. 28, 2006 anddesignating the US, which claims priority to US provisional applicationNo. 60/721,916, filed Sep. 29, 2005, each of which is hereinincorporated by reference in its entirety.

SEQUENCE LISTING

The instant application contains a Sequence Listing which has beensubmitted in ASCII format via EFS-Web, and is hereby incorporated byreference in its entirety. The ASCII copy, is named“149P_PCT2_USA_SEQ_LISTING_ST25.txt”, created on Feb. 23, 2015, and hasthe file size of 228,000 bytes.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention is directed to methods for stimulating themotility of the gastrointestinal system in a patient which comprisesadministering peptidyl analogs that possess agonistic ghrelin activity,a prodrug thereof, or a pharmaceutically acceptable salt of said analogsor said prodrug.

Description of the Related Art

Gastrointestinal (GI) motility is a coordinated neuromuscular processthat transports nutrients through the digestive system (Scarpignato, C.,Dig. Dis., (1997), 15:112), the impairment of which may result in avariety of ailments including gastroesophageal reflux disease (GERD),gastroparesis (e.g., diabetic and post-surgical), irritable bowelsyndrome (IBS), constipation (e.g. that associated with the hypomotilityphase of IBS), emesis (e.g., that caused by cancer chemotherapy agents),ileus and colonic pseudo-obstruction (U.S. Pat. No. 6,548,501; U.S.Patent Application No. 20040266989). These various complications ofinterrupted GI motility contribute significantly to the health careburdens of industrialized nations (U.S. Pat. No. 6,548,501; Feighner, S.D. et al., Science, (1999), 284:2184-8).

“Ileus” refers to the obstruction of the bowel or gut, especially thecolon (see, e.g., Dorland's Illustrated Medical Dictionary, p. 816, 27thed. (W.B. Saunders Company, Philadelphia 1988)). Generally, any traumato the bowel resulting in the release of inflammatory mediators leadingto activation of inhibitory neural reflexes will result in the onset ofileus. Ileus may be diagnosed by the disruption of the normalcoordinated movements of the gut, resulting in failure of the propulsionof intestinal contents (Resnick, J., Am. J. of Gastroentero., (1997),92:751; Resnick, J., Am. J. of Gastroentero., (1997), 92:934). Ileusshould be distinguished from constipation, which refers to infrequent ordifficulty in evacuating the feces (see, e.g., Dorland's IllustratedMedical Dictionary, p. 375, 27th ed. (W.B. Saunders Company,Philadelphia 1988)).

Ileus may be brought about by a variety of causes such as parturition;intestinal ischaemia; retroperitoneal haematoma; intraabdominal sepsis;intraperitoneal inflammation, e.g., acute appendicitis, choecystitis,pancreatitis; fractures of the spine; ureteric colic; thoracic lesions;basal pneumonia; rib fractures; myocardial infarction; and metabolicdisturbances. Post-partum ileus is a common problem for women in theperiod following childbirth and is thought to be caused by fluctuationsin natural opioid levels as a result of birthing stress. Patients havingundergone procedures such as major abdominal surgery includinglaparotomy for abdominal abscess or small intestinal transplantation(SITx), chest, pelvic or orthopedic surgery, often suffer from a periodof transient impairment of bowel function called post-surgical orpost-operative ileus (referred to hereinafter as POI).

POI commonly occurs for 24 to 72 hours following surgery. In someinstances, the bowel dysfunction may become quite severe, lasting formore than a week and affecting more than one portion of the GI tract(Livingston, E. H. et al., Digest. Dis. and Sci., (1990), 35:121).Gastrointestinal dysmotility associated with POI is generally mostsevere in the colon. POI is characterized by abdominal nausea,distension, vomiting, obstipation, inability to eat and cramps. POI notonly delays the normal resumption of food intake after surgery andprolongs hospitalization, but also fosters postoperative complications,especially aspiration pneumonia.

The administration of opioid analgesics to a patient after surgery mayoften contribute to and/or exacerbate existing bowel dysfunction,thereby delaying recovery of normal bowel function. Since virtually allpatients receive opioid analgesics, such as morphine or other narcoticsfor pain relief after surgery, particularly major surgery, currentpost-surgical pain treatment may actually slow recovery of normal bowelfunction, resulting in a delay in hospital discharge and increasing thecost of medical care.

Agents which act to affect gastrointestinal motility may also conferbeneficial effects upon patients suffering from emesis. Emesis, orvomiting, is often preceded by retching and may be accompanied by dryheaves. Emesis may be caused by imbalances in the digestive tract, suchas ileus, dyspepsia, or inflammation of the gastric wall, or byimbalances in the sensory system or brain, such as motion sickness,migraine or tumors. Emesis may be self-induced such as in anorexia orbulimia, and it may also occur in response to severe pain, emotionalresponses (e.g., to disagreeable sights or odors), or pregnancy. Emesisis a common complication following the administration of manymedications, particularly anti-cancer treatments such as chemotherapy.Prolonged episodes or repetitive emesis may result in a variety ofinjuries to the organism, including dehydration and electrolyteimbalances (Quigley, E. M. et al., Gastroentero., (2001), 120:263-86).

Agents which act to affect gastrointestinal motility may also conferbeneficial effects upon patients suffering from gastroparesis.Gastroparesis, also called delayed gastric emptying, is a disorder inwhich the nerves to the stomach are damaged or stop working and thestomach takes too long to empty its contents. For example, followingdamage to the vagus nerve, the nerve which controls the movement of foodthrough the digestive tract, the muscles of the stomach and intestinesdo not work normally and the movement of food is slowed or stopped. Highblood glucose causes chemical changes in nerves and damages the bloodvessels that carry oxygen and nutrients to the nerves. If blood glucoselevels remain high over a long period of time, as is often the case indiabetes, the vagus nerve can be damaged; gastroparesis often occurs inpeople with type 1 diabetes or type 2 diabetes (Murray, C. D. et al.,Gut, (2005), 54:1693-8).

The traditional therapies for impaired GI motility, such as that ofileus, gastroparesis and emesis, are considered ineffective. Currenttherapies for treating ileus include functional stimulation of theintestinal tract, stool softeners, laxatives such as Dulcolax®,lubricants, intravenous hydration, nasogastric suction, prokineticagents, early enteral feeding, and nasogastric decompression.Nasogastric intubation to decompress the stomach has also traditionallybeen used to treat ileus.

Traditional pharmaceuticals used to treat impaired GI motility, such asthat of ileus, include drugs that act to increase colonic motility, suchas Leu13-motilin and prostaglandin F2 alpha, and prokinetic agents, suchas Cisapride®. PROPULSID®, which contains Cisapride® monohydrate, is anoral gastrointestinal agent (U.S. Pat. No. 4,962,115) indicated for thesymptomatic treatment of adult patients with nocturnal heartburn due togastroesophageal reflux disease. Other prokinetic agents include, forexample, metoclopramide, domperidone, ondansetron, tropisetron,mosapride and itopride. Other treatments include administeringadenosine-antagonizing pyrazolopyridine compounds (U.S. Pat. No.6,214,843); pituitary adenylate cyclase activating peptide (PACAP)receptor antagonist in combination with a vasoactive intestinal peptide(VIP) receptor antagonist (U.S. Pat. No. 6,911,430); fedotozine (U.S.Pat. No. 5,362,756); neuropeptides (U.S. Pat. No. 5,929,035); andproteinase-activated receptor-2 antagonists (U.S. Pat. No. 5,929,035).In extreme cases, ileus has been treated with surgical intervention tounblock the colon.

These therapeutic regimens, however, suffer from numerous problems. Forinstance, PROPULSID® was recently removed from the market due to itspotential to induce cardiac arrhythmias (U.S. Pat. No. 6,548,501).Adolor Corporation is presently in phase III clinical trials for atherapy to treat postoperative ileus using Alvimopan (Entereg®).Adolor's therapy, however, utilizes opioid receptor antagonists whichmerely block the side effects of opiate analgesics, rather than actuallyrelieving the ileus condition. The phase III trials demonstrate marginalefficacy and minimal applicability for the treatment of ileus,particularly postoperative ileus.

Furthermore, these prior art methods for treatment of impaired GImotility lack specificity for different types of impairments, e.g.,postoperative ileus or post-partum ileus. Also, these prior art methodsoffer no means for the prevention of impaired GI motility, such as thatof ileus, gastroparesis and emesis. If impaired GI motility, such asthat of ileus, gastroparesis and emesis, could be prevented or moreeffectively treated, hospital stays, recovery times, and medical costswould be significantly decreased with the additional benefit ofminimizing patient discomfort.

Drugs which selectively target gut motility to correct gastrointestinaldysfunction caused by postoperative ileus would be ideal candidates forpreventing and/or treating post-surgical and post-partum ileus. Suchdrugs would also be excellent candidates for the treatment ofgastroparesis and/or emesis, particularly emesis associated withchemotherapies or other drug induced gastrointestinal dysfunction. Ofthose, drugs that do not interfere with the effects of opioid analgesicswould be of special benefit in that they may be administeredsimultaneously with drugs for pain management with limited side effects.

Peptides affecting the release of growth hormone (GH) are now thought toexhibit gastrokinetic or “prokinetic” effects (U.S. Pat. No. 6,548,501;Peeters, T. L., J Physiol. Pharmacol., (2003), 54 (supp 4):95-103 andreferences therein; Trudel, L. et al, J. Physiol. Gastrointest. LiverPhysiol., (2002), 282:G948-52). Such growth hormone-releasing peptides,or GHRPs, are also referred to as growth hormone secretagogues (GHS).Exemplary growth hormone-releasing peptides (GHRPs) believed to exhibitprokinetic effects include GHRP-1, GHRP-2 and ghrelin.

Ghrelin, a recently discovered orexigenic hormone, is produced as apreprohormone that is proteolytically processed to yield a peptide ofthe following sequence:H-Gly-Ser-Ser-Phe-Leu-Ser-Pro-Glu-His-Gln-Arg-Val-Gln-Gln-Arg-Lys-Glu-Ser-Lys-Lys-Pro-Pro-Ala-Lys-Leu-Gln-Pro-Arg-NH2(Kojima, M. et al., Nature, (1999), 402(6762):656-60; (SEQ ID NO:338)).Ghrelin is produced by epithelial cells lining the fundus of the stomachand functions to stimulate appetite; its levels increase prior to a mealand decrease thereafter.

Ghrelin powerfully stimulates GH secretion from the anterior pituitarygland, mainly at the hypothalamic level, through its interaction withgrowth hormone secretagoue receptor (GHS-R) both in animals and inhumans (Ukkola, O. et al., 2002 Ann. Med., (2002), 34:102-8; (Kojima, M.et al., Nature, (1999), 402(6762):656-60).

The native structures of ghrelin from several mammalian andnon-mammalian species are known (Kaiya, H. et al., J. of Biol. Chem.,(2001), 276:40441-8 and International Patent Application PCT/JP00/04907[WO 01/07475]). A core region present in ghrelin is responsible forobserved activity at the GHS receptor. The core region comprises thefour N-terminal amino acids wherein the serine in the third position isnormally modified with n-octanoic acid. In addition to acylation byn-octanoic acid, native ghrelin may also be acylated with n-decanoicacid (Kaiya, H. et al., J. of Biol. Chem., (2001), 276:40441-8).

Prior to the discovery that ghrelin is a native ligand for the GHSreceptor, it was known that GHRPs controlled the release of growthhormone from the pituitary somatotrops. The hexapeptideHis-D-Trp-Ala-Trp-D-Phe-Lys-amide (GHRP-6; (SEQ ID NO:342)), was foundto release growth hormone from the somatotrops in a dose-dependentmanner in several species including man (Bowers, C. Y. et al.,Endocrinology, (1984), 114(5):1537-45). Subsequent chemical studies onGHRP-6 led to the identification of other potent, synthetic GHSs such asGHRP-1, GHRP-2 and hexarelin (Cheng, K. et al., Endocrinology, (1989),124(6):2791-8; Bowers, C. Y., Novel GH-Releasing Peptides, Molecular andClinical Advances in Pituitary Disorders, Ed: Melmed, S., EndocrineResearch and Education, Inc., Los Angeles, Calif., USA, (1993), 153-7;and Deghenghi, R. et al., Life Sci., (1994), 54(18):1321-8). Thestructures of these compounds are as shown:

GHRP-1 (SEQ ID NO: 339) Ala-His-D-(2′)-Nal-Ala-Trp-D-Phe-Lys-NH₂; GHRP-2(SEQ ID NO: 340) D-Ala-D-(2′)-Nal-Ala-Trp-D-Nal-Lys-NH₂; and Hexarelin(SEQ ID NO: 341) His-D-2-MeTrp-Ala-Trp-D-Phe-Lys-NH₂.GHRP-1, GHRP-2, GHRP-6, and hexarelin are classified as synthetic GHSs.

A number of recent studies have demonstrated the potential use of GHSssuch as ghrelin, GHRP-6 and others to stimulate motor activity in theintestinal tract and to treat conditions such as ileus and emesis. Forexample, ghrelin and GHRP-6 have been shown to accelerate gastricemptying in rats and mice (Peeters, T. L., J Physiol. Pharmacol.,(2003), 54 (supp 4):95-103). In rats, ghrelin has been shown to reversethe delay of gastric emptying in a post-operative ileus model (Peeters,T. L., J Physiol. Pharmacol., (2003), 54 (supp 4):95-103; Trudel, L. etal., J. Physiol. Gastrointest. Liver Physiol., (2002), 282(6):G948-52)and in laparectomized dogs, ghrelin was shown to improve POI in thetreated animals (Trudel, L. et al, Peptides, (2003), 24:531-4). Inseptic mice, ghrelin and GHRP-6 accelerated gastric emptying althoughhad little effect upon increasing transit in the small intestine (DeWinter, B. Y. et al., Neurogastroenterol. Motil., (2004), 16:439-46).

In experiments designed to mimic hospitalization conditions for a humanpatient experiencing POI, laparectomized rats were exposed to opiates aswell as ghrelin analog RC-1139 (Poitras, P. et al., Peptides, (2005),26:1598-601). In an assay measuring gastric empyting, RC-1139 was shownto reverse POI in the control and laparectomized rats in the presence ofmorphine. It is thus believed that ghrelin exhibits gastrokineticeffects without interfering with opiate activity.

Ferrets exposed to the cytotoxic anti-cancer agent cisplatin exhibitedsignificantly reduced occurrences of retching and vomiting followingintracerebroventricular administration of ghrelin (Rudd, J. A. et at,Neurosci. Lett., (2006), 392:79-83) thus confirming the ability ofghrelin to reduce emesis in a manner consistent with its role inmodulating gastro-intestinal functions. It is thought that ghrelin'srole in modulating gastric motility is independent of the GH-secretoryactivation and may be mediated by the vagal-cholinergic muscarinicpathway (U.S. Patent Application No. 20060025566).

Ghrelin has also been shown to increase gastric emptying in patientswith diabetic gastroparesis (Murray, C. D. et al., Gut, (2005),54:1693-8).

It is interesting to note that in the studies referenced above, theghrelin or ghrelin analog was administered using intraperitoneal (ip),intravenous (iv) or intracerebroventricular (icy) injection. Otherdisclosures (U.S. Pat. No. 6,548,501; U.S. Patent Application No.20020042419; U.S. Patent Application No. 20050187237; U.S. PatentApplication No. 20060025566) report on the oral administration of GHSsas a means to treat impaired gastrointestinal motility.

Very few compounds are known in the art to be useful for treatingimpaired GI motility and more compounds affecting gastrointestinalmotility, e.g. stimulation of motility, would be highly desirable.Compounds affecting gastrointestinal kinetics are useful in thetreatment of interruptions in normal GI functions such as ileus andemesis.

SUMMARY OF THE INVENTION

The present invention relates to a method of stimulatinggastrointestinal motility in a patient (e.g., a mammal such as a human).The method includes the step of administering a therapeuticallyeffective amount of a peptidyl analog of ghrelin to said patientexperiencing or at risk of experiencing gastrointestinal dysmotility.

In one aspect, the present invention provides a method of treatinggastrointestinal dysmotility conditions by administering atherapeutically effective amount of a peptidyl analog of ghrelin orprodrug thereof suitable for attenuating such gastrointestinalconditions where the analog or prodrug comprises a compound according toFormula (I), Formula (II) or Formula (III), or a pharmaceuticallyacceptable salt thereof. The method of the invention is useful forpromoting gastric and gastrointestinal motility in a patient (e.g., amammal such as a human) and as such, is useful for treating conditionsbenefiting from improved gastric and gastrointestinal motility such asgastroesophageal reflux disease (GERD), IBS, constipation, ileus,emesis, gastroparesis, colonic pseudo-obstruction, and the like.

In another aspect, the invention provides a method of treating ileus,gastroparesis or emesis by administering a therapeutically effectiveamount of a peptidyl analog of ghrelin suitable for attenuating ileus,emesis, or gastroparesis. In yet another aspect, the condition treatedby the method of the invention is ileus, such as post-operative ileusand the operation may be a gastrointestinal surgery. In yet anotheraspect of the invention, the condition treated by the method of theinvention is emesis, such as emesis associated with or provoked by theadministration of an anti-cancer chemotherapeutic agent. In yet anotheraspect, the condition treated by the method of the invention isgastroparesis, such as diabetic gastroparesis. The diabetes may be TypeI or Type II diabetes.

In one aspect, the invention provides a method of treatinggastrointestinal conditions such as GERD, IBS, constipation, ileus,emesis, gastroparesis, and colonic pseudo-obstruction and the like, byadministering a therapeutically effective amount of a peptidyl ghrelinanalog according to the following formula (I):

(R²R³)-A¹-A²-A³-A⁴-A⁵-A⁶-A⁷-A⁸-A⁹-A¹⁰-A¹¹-A¹²-A¹³-A¹⁴-A¹⁵-A¹⁶-A¹⁷-A¹⁸-A¹⁹-A²⁰-A²¹-A²²-A²³-A²⁴-A²⁵-A²⁶-A²⁷-A²⁸-R¹

wherein:

A¹ is Gly, Aib, Ala, β-Ala, or Acc;

A² is Ser, Aib, Act, Ala, Acc, Abu, Ava, Thr, or Val;

A³ is Ser, Ser(C(O)—R⁴), Asp(O—R⁸), Asp(NH—R⁹), Cys(S—R¹⁴),Dap(S(O)₂—R¹⁰) Dab(S(O)₂—R¹¹), Glu(O—R⁶), Glu(NH—R⁷), Thr, Thr(C(O)—R⁵),or HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O);

A⁴ is Phe, Acc, Aic, Cha, 2-Fua, 1-Nal, 2-Nal, 2-Pal, 3-Pal, 4-Pal,hPhe, (X¹,X²,X³,X⁴,X⁵)Phe, Taz, 2-Thi, 3-Thi, Trp, or Tyr;

A⁵ is Leu, Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle, orVal;

A⁶ is Ser, Abu, Acc, Act, Aib, Ala, Gly, Thr, or Val;

A⁷ is Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, ordeleted;

A⁸ is Glu, Acc, Aib, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted;

A⁹ is His, Apc, Aib, Acc, 2-Fua, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi,(X¹,X²,X³,X⁴,X⁵-)Phe or deleted;

A¹⁰ is Gln, Acc, Aib, Asn, Asp, Glu, or deleted;

A¹¹ is Arg, Apc, hArg, Dab, Dap, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted;

A¹² is Val, Abu, Acc, Aib, Ala, Cha, Nva, Gly, Ile, Leu, Nle, Tle, ordeleted;

A¹³ is Gln, Acc, Aib, Asn, Asp, Glu, or deleted;

A¹⁴ is Gln, Acc, Aib, Asn, Asp, Glu, or deleted;

A¹⁵ is Arg, hArg, Acc, Aib, Apc, Dab, Dap, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted;

A¹⁶ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted;

A¹⁷ is Glu, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted;

A¹⁸ is Ser, Abu, Acc, Act, Aib, Ala, Thr, Val, or deleted;

A¹⁹ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted;

A²⁰ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted;

A²¹ is Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, ordeleted;

A²² is Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, ordeleted;

A²³ is Abu, Acc, Act, Aib, Ala, Apc, Gly, Nva, Val, or deleted;

A²⁴ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted;

A²⁵ is Leu, Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle, Val,or deleted;

A²⁶ is Gln, Aib, Asn, Asp, Glu, or deleted;

A²⁷ is Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, ordeleted;

A²⁸ is Acc, Aib, Apc, Arg, hArg, Dab, Dap, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted;

R¹ is —OH, —NH₂, —(C₁-C₃₀)alkoxy, or NH—X⁶—CH₂—Z⁰, wherein X⁶ is a(C₁-C₁₂)alkyl, (C₂-C₁₂)alkenyl, and Z⁰ is —H, —OH, —CO₂H or —C(O)—NH₂;

R² and R³ each is, independently for each occurrence, H, (C₁-C₂₀)alkylor (C₁-C₂₀)acyl;

R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹ and R¹⁴ each is, independently for eachoccurrence, (C₁-C₄₀)alkyl, (C₂-C₄₀)alkenyl, substituted (C₁-C₄₀) alkyl,substituted (C₂-C₄₀) alkenyl, alkylaryl, substituted alklyaryl, aryl orsubstituted aryl;

R¹² and R¹³ each is, independently for each occurrence, H,(C₁-C₄₀)alkyl, (C₁-C₄₀)acyl, (C₁-C₃₀)alkylsulfonyl, or —C(NH)—NH₂,wherein when R¹² is (C₁-C₄₀)acyl, (C₁-C₃₀)alkylsulfonyl, or —C(NH)—NH₂,then R¹³ is H or (C₁-C₁₀)alkyl;

n is, independently for each occurrence, 1, 2, 3, 4 or 5;

X¹, X², X³, X⁴, and X⁵ each is, independently for each occurrence, H, F,Cl, Br, I, (C₁₋₁₀)alkyl, substituted (C₁₋₁₀)alkyl, aryl, substitutedaryl, OH, NH₂, NO₂, or CN;

provided that the peptide contains at least one amino acid selected fromthe groups consisting of:

A² is Aib, Acc, or Act;

A³ is Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹), Glu(NH-Hexyl), or Cys(S-Decyl);

A⁵ is Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle, or Val;

A⁶ is Abu, Acc, Act, Aib, Ala, Gly, Thr or Val;

A⁷ is Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz or Tic;

A⁸ is Acc, Aib, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn, orHN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O);

A⁹ is Aib, Acc, Apc, 2-Fua, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi, or(X¹,X²,X³,X⁴, X⁵-)Phe; and

A¹⁰ is Acc, Aib, Asn, Asp, or Glu;

and further provided that the peptide is not (Lys⁸)hGhrelin(1-8)-NH₂ or(Arg⁸)hGhrelin(1-8)-NH₂; or a pharmaceutically acceptable salt thereof.

In another aspect, the invention provides a preferred group of compoundsaccording to formula (I), wherein:

A¹ is Gly or Aib;

A² is Ser, Aib, A5c, Act, or Ava;

A³ is Ser(C(O)—R⁴), Glu(O—R⁶), Glu(NH—R⁷), Dap(S(O)₂—R¹⁰), orDab(S(O)₂—R¹¹);

A⁴ is Phe;

A⁵ is Leu, Acc, Aib, Cha, or hLeu;

A⁶ is Ser, Abu, Act, Aib, or Thr;

A⁷ is Pro, Dhp, Dmt, 4-Hyp, Ktp, Pip, Tic, or Thz;

A⁸ is Glu or Aib;

A⁹ is His, Aib, Apc, 2-Fua, 2-Pal, 3-Pal, 4-Pal, Taz, or 2-Thi;

A¹⁰ is Gln or Aib;

A¹¹ is Arg;

A¹² is Aib, Val or Acc;

A¹³ is Gln;

A¹⁴ is Gln;

A¹⁵ is Arg or Orn;

A¹⁶ is Lys or Apc;

A¹⁷ is Glu;

A¹⁸ is Ser;

A¹⁹ is Lys;

A²⁰ is Lys;

A²¹ is Pro;

A²² is Pro;

A²³ is Ala;

A²⁴ is Lys;

A²⁵ is Leu;

A²⁶ is Gln;

A²⁷ is Pro; and

A²⁸ is Arg, or a pharmaceutically acceptable salt thereof.

In yet another aspect, the invention provides a preferred group ofcompounds according to formula (I), wherein:

R² and R³ each is, independently, H, Acyl, n-butyryl, isobutyryl, orn-octanoyl;

R⁴ is octyl;

R⁶ is hexyl;

R⁷ is hexyl;

R¹⁰ is octyl; and

R¹¹ is octyl, or a pharmaceutically acceptable salt thereof, wherein Accis, independently for each occurrence, A5c or A6c.

In yet another aspect, the invention provides a preferred group ofcompounds according to formula (I), where the compound is:

(SEQ ID NO: 1) (Dap³(octanesulfonyl))hGhrelin(1-28)-NH₂; Example #75(SEQ ID NO: 2) (Aib², A6c⁵)hGhrelin(1-28)-NH₂; Example #96(SEQ ID NO: 3) (A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 4)(Aib^(2,6))hGhrelin(1-28)-NH₂; Example #108 (SEQ ID NO: 5)(Aib², A5c¹²)hGhrelin(1-28)-NH₂; (SEQ ID NO: 6)(Aib², A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 7)(Aib², A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 7)(Aib², Act⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 8)(Aib², 3-Pal⁹)hGhrelin(1-28)-NH₂; Example #29 (SEQ ID NO: 9)(Aib², Dmt⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 9)(Aib², Thz⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 10)(A5c²)hGhrelin(1-28)-NH₂; Example #52 (SEQ ID NO: 10)(Act²)hGhrelin(1-28)-NH₂; Example #94 (SEQ ID NO: 2)(Aib², A5c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 2)(Aib², A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 2)(Aib^(2,5))hGhrelin(1-28)-NH₂; (SEQ ID NO: 2)(Aib², hLeu⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 2)(Aib², Cha⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 4)(Aib^(2,6))hGhrelin(1-28)-NH₂; (SEQ ID NO: 4)(Aib², Act⁶)hGhrelin(1-28)-NH₂; Example #114 (SEQ ID NO: 4)(Aib², Thr⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 4)(Aib², Abu⁶)hGhrelin(1-28)-NH₂; Example #88 (SEQ ID NO: 9)(Aib², 4-Hyp⁷)hGhrelin(1-28)-NH₂; Example #36 (SEQ ID NO: 9)(Aib², Thz⁷)hGhrelin(1-28)-NH₂; Example #54 (SEQ ID NO: 9)(Aib², Pip⁷)hGhrelin(1-28)-NH₂; Example #65 (SEQ ID NO: 9)(Aib², Dhp⁷)hGhrelin(1-28)-NH₂; Example #44 (SEQ ID NO: 9)(Aib², Ktp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 11)(Aib^(2,8))hGhrelin(1-28)-NH₂; Example #49 (SEQ ID NO: 8)(Aib², 2-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 8)(Aib², 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 8)(Aib², 4-Pal⁹)hGhrelin(1-28)-NH₂; Example #55 (SEQ ID NO: 8)(Aib², Taz⁹)hGhrelin(1-28)-NH₂; Example #27 (SEQ ID NO: 8)(Aib², 2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 8)(Aib², 2-Fua⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 8)(Aib², Apc⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 8)(Aib^(2,9))hGhrelin(1-28)-NH₂; (SEQ ID NO: 12)(Aib^(2,10))hGhrelin(1-28)-NH₂; Example #48 (SEQ ID NO: 9)(Aib², Tic⁷)hGhrelin(1-28)-NH₂; Example #53 (SEQ ID NO: 13)(Aib⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 3) (A5c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 3) (A6c⁵)hGhrelin(1-28)-NH₂; Example #102 (SEQ ID NO: 13)(Act⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 14)(3-Pal⁹)hGhrelin(1-28)-NH₂; Example #32 (SEQ ID NO: 15)(Dmt⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 15) (Thz⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 3) (Aib⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 3)(hLeu⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 3) (Cha⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 13) (Thr⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 13)(Abu⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 15) (4-Hyp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 15) (Pip⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 15)(Dhp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 15) (Ktp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 16) (Aib⁸)hGhrelin(1-28)-NH₂; Example #10 (SEQ ID NO: 14)(2-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 14) (3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 14) (4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 14)(Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 14)(2-Thi⁹)hGhrelin(1-28)-NH₂; Example #26 (SEQ ID NO: 14)(2-Fua⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 14) (Apc⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 14) (Aib⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 17)(Aib¹⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO: 18)(Aib², Dap³(octanesulfonyl), A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 19)(Dap³(octanesulfonyl), A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 20)(Aib^(2,6), Dap³(octanesulfonyl))hGhrelin(1-28)-NH₂; (SEQ ID NO: 21)(Aib², Dap³(octanesulfonyl), A5c¹²)hGhrelin(1-28)-NH₂; (SEQ ID NO: 22)(Aib², Dap³(octanesulfonyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 23)(Aib², Dap³(octanesulfonyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 20) (Aib², Dap³(octanesulfonyl), Act⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 24) (Aib², Dap³(octanesulfonyl), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 25) (Aib², Dap³(octanesulfonyl), Dmt⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 25) (Aib², Dap³(octanesulfonyl), Thz⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 26) (A5c², Dap³(octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO: 26) (Act², Dap³(octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO: 18) (Aib², Dap³(octanesulfonyl), A5c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 18) (Aib^(2,5), Dap³(octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO: 18) (Aib², Dap³(octanesulfonyl), hLeu⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 18) (Aib², Dap³(octanesulfonyl), Cha⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 20) (Aib^(2,6), Dap³(octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO: 20) (Aib², Dap³(octanesulfonyl), Thr⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 20) (Aib², Dap³(octanesulfonyl), Abu⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 25) (Aib², Dap³(octanesulfonyl), 4-Hyp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 25) (Aib², Dap³(octanesulfonyl), Pip⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 25) (Aib², Dap³(octanesulfonyl), Dhp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 25) (Aib², Dap³(octanesulfonyl), Ktp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 27) (Aib^(2,8), Dap³(octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO: 24) (Aib², Dap³(octanesulfonyl), 2-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 24) (Aib², Dap³(octanesulfonyl), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 24) (Aib², Dap³(octanesulfonyl), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 24) (Aib², Dap³(octanesulfonyl), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 24) (Aib², Dap³(octanesulfonyl), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 24) (Aib², Dap³(octanesulfonyl), 2-Fua⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 24) (Aib², Dap³(octanesulfonyl), Apc⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 24) (Aib^(2,9), Dap³(octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO: 28) (Aib^(2,10), Dap³(octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO: 19) (Dap³(octanesulfonyl), A6c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 29) (Dap³(octanesulfonyl), Aib⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 30) (Dap³(octanesulfonyl), A5c¹²)hGhrelin(1-28)-NH₂;(SEQ ID NO: 31) (Dap³(octanesulfonyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 32) (Dap³(octanesulfonyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 29) (Dap³(octanesulfonyl), Act⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 33) (Dap³(octanesulfonyl), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 34) (Dap³(octanesulfonyl), Dmt⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 34) (Dap³(octanesulfonyl), Thz⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 19) (Dap³(octanesulfonyl), A5c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 19) (Dap³(octanesulfonyl), Aib⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 19) (Dap³(octanesulfonyl), hLeu⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 19) (Dap³(octanesulfonyl), Cha⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 29) (Dap³(octanesulfonyl), Thr⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 29) (Dap³(octanesulfonyl), Abu⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 34) (Dap³(octanesulfonyl), 4-Hyp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 34) (Dap³(octanesulfonyl), Pip⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 34) (Dap³(octanesulfonyl), Dhp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 34) (Dap³(octanesulfonyl), Ktp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 35) (Dap³(octanesulfonyl), Aib⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO: 33) (Dap³(octanesulfonyl), 2-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 33) (Dap³(octanesulfonyl), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 33) (Dap³(octanesulfonyl), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 33) (Dap³(octanesulfonyl), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 33) (Dap³(octanesulfonyl), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 33) (Dap³(octanesulfonyl), 2-Fua⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 33) (Dap³(octanesulfonyl), Apc⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 36) (Dap³(octanesulfonyl), Aib¹⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO: 31) (Dap³(octanesulfonyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 31) (Dab³(octanesulfonyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 37) (Aib², A6c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 38) (A6c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 39)(Aib^(2,6), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 39)(Aib², Act⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 40)(Aib², 3-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 41)(Aib², Dmt⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 41)(Aib², Thz⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 37)(Aib², A5c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 37)(Aib^(2,5), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 37)(Aib², hLeu⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 37)(Aib², Cha⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 39)(Aib^(2,6), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 39)(Aib², Thr⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 39)(Aib², Abu⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 41)(Aib², 4-Hyp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 41)(Aib², Pip⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 41)(Aib², Dhp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 41)(Aib², Ktp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 42)(Aib^(2,8), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 40)(Aib², 2-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 40)(Aib², 3-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 40)(Aib², 4-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 40)(Aib², Taz⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 40)(Aib², 2-Thi⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 40)(Aib², 2-Fua⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 40)(Aib², Apc⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 40)(Aib^(2,9), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 43)(Aib^(2,10), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 32)(Dap³(octanesulfonyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 32)(Dab³(octanesulfonyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 44)(Aib², A6c⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 45)(A6c⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 46)(Aib^(2,6), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 46)(Aib², Act⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 47)(Aib², 3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 48)(Aib², Dmt⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 48)(Aib², Thz⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 44)(Aib², A5c^(5,12), Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 44)(Aib^(2,5), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 44)(Aib², hLeu⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 44)(Aib², Cha⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 46)(Aib^(2,6), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 46)(Aib², Thr⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 46)(Aib², Abu⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 48)(Aib², 4-Hyp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 48)(Aib², Pip⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 48)(Aib², Dhp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 48)(Aib², Ktp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 49)(Aib^(2,8), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 47)(Aib², 2-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 47)(Aib², 3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 47)(Aib², 4-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 47)(Aib², Taz⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 47)(Aib², 2-Thi⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 47)(Aib², 2-Fua⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 47)(Aib², Apc⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 47)(Aib^(2,9), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 50)(Aib^(2,10), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 38)(A6c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 51)(Aib⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 51)(Act⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 52)(3-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 53)(Dmt⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 53)(Thz⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 38)(A5c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 38)(Aib⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 38)(hLeu⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 38)(Cha⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 51)(Aib⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 51)(Thr⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 51)(Abu⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 53)(4-Hyp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 53)(Pip⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 53)(Dhp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 53)(Ktp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 54)(Aib⁸, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 52)(2-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 52)(3-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 52)(4-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 52)(Taz⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 52)(2-Thi⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 52)(2-Fua⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 52)(Apc⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 52)(Aib⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 55)(Aib¹⁰, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 56)(Aib⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 45)(A5c⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 56)(Act⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 57)(3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 58)(Dmt⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 58)(Thz⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 45)(Aib⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 45)(hLeu⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 45)(Cha⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 56)(Thr⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 56)(Abu⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 58)(4-Hyp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 58)(Pip⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 58)(Dhp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 58)(Ktp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 59)(Aib⁸, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 57)(2-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 57)(3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 57)(4-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 57)(Taz⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 57)(2-Thi⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 57)(2-Fua⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 57)(Apc⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 57)(Aib⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 60)(Aib¹⁰, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 61)(Aib², Glu³(NH-hexyl), A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 62)(Glu³(NH-hexyl), A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 63)(Aib^(2,6), Glu³(NH-hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO: 63)(Aib², Glu³(NH-hexyl), Act⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 64)(Aib², Glu³(NH-hexyl), 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 65)(Aib², Glu³(NH-hexyl), Dmt⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 65)(Aib², Glu³(NH-hexyl), Thz⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 61)(Aib², Glu³(NH-hexyl), A5c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 61)(Aib^(2,5), Glu³(NH-hexyl))hGhrelin(1-28)-NH2; (SEQ ID NO: 61)(Aib², Glu³(NH-hexyl), hLeu⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 2)(Aib², Cha⁵)hGhrelin(1-28)-NH₂; Example #81 (SEQ ID NO: 63)(Aib^(2,6), Glu³(NH-hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO: 63)(Aib², Glu³(NH-hexyl), Thr⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 63)(Aib², Glu³(NH-hexyl), Abu⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 65)(Aib², Glu³(NH-hexyl), 4-Hyp⁷)hGhrelin(1-28)-NH₂; Example #79(SEQ ID NO: 65) (Aib², Glu³(NH-hexyl), Pip⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 65) (Aib², Glu³(NH-hexyl), Dhp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 65) (Aib², Glu³(NH-hexyl), Ktp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 27)(Aib^(2,8), Glu³(NH-hexyl))hGhrelin(1-28)-NH₂; Example #56(SEQ ID NO: 64) (Aib², Glu³(NH-hexyl), 2-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 64)(Aib², Glu³(NH-hexyl), 3-Pal⁹)hGhrelin(1-28)-NH₂; Example #80(SEQ ID NO: 64)(Aib², Glu³(NH-hexyl), 4-Pal⁹)hGhrelin(1-28)-NH₂; Example #85(SEQ ID NO: 64) (Aib², Glu³(NH-hexyl), Taz⁹)hGhrelin(1-28)-NH₂; Example #43(SEQ ID NO: 64)(Aib², Glu³(NH-hexyl), 2-Thi⁹)hGhrelin(1-28)-NH₂; Example #51(SEQ ID NO: 64) (Aib², Glu³(NH-hexyl), 2-Fua⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 64) (Aib², Glu³(NH-hexyl), Apc⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 64) (Aib^(2,9), Glu³(NH-hexyl))hGhrelin(1-28)-NH₂;(SEQ ID NO: 28)(Aib^(2,10), Glu³(NH-hexyl))hGhrelin(1-28)-NH₂; Example #59(SEQ ID NO: 66) (Glu³(NH-hexyl), Aib⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 62) (Glu³(NH-hexyl), A5c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 66) (Glu³(NH-hexyl), Act⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 67) (Glu³(NH-hexyl), 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 68) (Glu³(NH-hexyl), Dmt⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 68) (Glu³(NH-hexyl), Thz⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 62) (Glu³(NH-hexyl), Aib⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 62) (Glu³(NH-hexyl), hLeu⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 62) (Glu³(NH-hexyl), Cha⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 66) (Glu³(NH-hexyl), Thr⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 66) (Glu³(NH-hexyl), Abu⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 68) (Glu³(NH-hexyl), 4-Hyp⁷)hGhrelin(1-28)-NH₂; Example #82(SEQ ID NO: 68) (Glu³(NH-hexyl), Pip⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 68) (Glu³(NH-hexyl), Dhp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 68) (Glu³(NH-hexyl), Ktp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 35) (Glu³(NH-hexyl), Aib⁸)hGhrelin(1-28)-NH₂; Example #35(SEQ ID NO: 67) (Glu³(NH-hexyl), 2-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 67) (Glu³(NH-hexyl), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 67) (Glu³(NH-hexyl), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 67) (Glu³(NH-hexyl), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 67) (Glu³(NH-hexyl), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 67) (Glu³(NH-hexyl), 2-Fua⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 67) (Glu³(NH-hexyl), Apc⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 67) (Glu³(NH-hexyl), Aib⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 36) (Glu³(NH-hexyl), Aib¹⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO: 69)(Aib², Glu³(NH-hexyl), A6c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  70) (A6c⁵, Glu³(NH-hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 71)(Aib^(2,6), Glu³(NH-hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  71)(Aib², Glu³(NH-hexyl), Act⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 72)(Aib², Glu³(NH-hexyl), 3-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  73)(Aib², Glu³(NH-hexyl), Dmt⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 73)(Aib², Glu³(NH-hexyl), Thz⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 69)(Aib², Glu³(NH-hexyl), A5c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 69)(Aib^(2,5), Glu³(NH-hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 37) (Aib², hLeu⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 69)(Aib², Glu³(NH-hexyl), Cha⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 71)(Aib^(2,6), Glu³(NH-hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 71)(Aib², Glu³(NH-hexyl), Thr⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 71)(Aib², Glu³(NH-hexyl), Abu⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 73)(Aib², Glu³(NH-hexyl), 4-Hyp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 73)(Aib², Glu³(NH-hexyl), Pip⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 73)(Aib², Glu³(NH-hexyl), Dhp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 73)(Aib², Glu³(NH-hexyl), Ktp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 74)(Aib^(2,8), Glu³(NH-hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 72)(Aib², Glu³(NH-hexyl), 2-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 72)(Aib², Glu³(NH-hexyl), 3-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 72)(Aib², Glu³(NH-hexyl), 4-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 72)(Aib², Glu³(NH-hexyl), Taz⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 72)(Aib², Glu³(NH-hexyl), 2-Thi⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 72)(Aib², Glu³(NH-hexyl), 2-Fua⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 72)(Aib², Glu³(NH-hexyl), Apc⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 72)(Aib^(2,9), Glu³(NH-hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  75)(Aib^(2,12), Glu³(NH-hexyl), 4-Pal⁹, Orn¹⁵)hGhrelin(1-28)-NH₂; Example #89(SEQ ID NO: 76)(Aib^(2,10), Glu³(NH-hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 77)(Aib², Glu³(NH-hexyl), A6c⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 78) (Glu³(NH-hexyl), A6c⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 79)(Aib^(2,6), Glu³(NH-hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 79)(Aib², Glu³(NH-hexyl), Act⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 80)(Aib², Glu³(NH-hexyl), 3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 81)(Aib², Glu³(NH-hexyl), Dmt⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 81)(Aib², Glu³(NH-hexyl), Thz⁷, A5C¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 77)(Aib², Glu³(NH-hexyl), A5c^(5,12), Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 77)(Aib^(2,5), Glu³(NH-hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  77)(Aib², Glu³(NH-hexyl), hLeu⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  77)(Aib², Glu³(NH-hexyl), Cha⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 79)(Aib^(2,6), Glu³(NH-hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 79)(Aib², Glu³(NH-hexyl), Thr⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 79)(Aib², Glu³(NH-hexyl), Abu⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 81)(Aib², Glu³(NH-hexyl), 4-Hyp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 81)(Aib², Glu³(NH-hexyl), Pip⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 81)(Aib², Glu³(NH-hexyl), Dhp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 81)(Aib², Glu³(NH-hexyl), Ktp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 82)(Aib^(2,8), Glu³(NH-hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 80)(Aib², Glu³(NH-hexyl), 2-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 80)(Aib², Glu³(NH-hexyl), 3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 80)(Aib², Glu³(NH-hexyl), 4-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 80)(Aib², Glu³(NH-hexyl), Taz⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 80)(Aib², Glu³(NH-hexyl), 2-Thi⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 80)(Aib², Glu³(NH-hexyl), 2-Fua⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 80)(Aib², Glu³(NH-hexyl), Apc⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 80)(Aib^(2,9), Glu³(NH-hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 83)(Aib^(2,10), Glu³(NH-hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 1) (Glu³(O-hexyl))hGhrelin(1-28)-NH₂; Example #21(SEQ ID NO: 10) (Aib²)hGhrelin(1-28)-NH₂; Example #25 (SEQ ID NO: 1)(Glu³(NH-hexyl))hGhrelin(1-28)-NH₂; Example #76 (SEQ ID NO: 84)(Aib², Glu³(O-hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO: 85)(Aib¹, Glu³(O-hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO: 84)(Aib², Glu³(NH-hexyl))hGhrelin(1-28)-NH₂; Example #8 (SEQ ID NO: 1)(Dap³(1-octanesulfonyl))hGhrelin(1-28)-NH₂; (SEQ ID NO: 84)(Aib², Dap³(1-octanesulfonyl))hGhrelin(1-28)-NH₂; (SEQ ID NO: 85)(Aib¹, Dap³(1-octanesulfonyl))hGhrelin(1-28)-NH₂; (SEQ ID NO: 86)(Ava2, Dap³(1-octanesulfonyl))hGhrelin(2-28)-NH₂; (SEQ ID NO: 87)(Ac-Gly¹)hGhrelin(1-5)-NH₂; (SEQ ID NO: 88) (Ac-Gly¹)hGhrelin(1-6)-NH₂;(SEQ ID NO: 89) (Ac-Gly¹)hGhrelin(1-7)-NH₂; (SEQ ID NO: 90)(Ac-Gly¹, Aib²)hGhrelin(1-28)-NH₂; Example #63 (SEQ ID NO: 91)(Ac-Gly¹, Aib², Glu³(NH-hexyl))hGhrelin(1-5)-NH₂; (SEQ ID NO: 92)(Ac-Gly¹, Aib², Glu³(NH-hexyl))hGhrelin(1-6)-NH₂; (SEQ ID NO: 93)(Ac-Gly¹, Aib², Glu³(NH-hexyl))hGhrelin(1-7)-NH₂; (SEQ ID NO: 94)(Ac-Gly¹, Aib², Glu³(NH-hexyl), Arg⁸)hGhrelin(1-8)-NH₂; (SEQ ID NO: 94)(Ac-Gly¹, Aib², Glu³(NH-hexyl), Lys⁸)hGhrelin(1-8)-NH₂; (SEQ ID NO: 95)(n-butyryl-Gly¹)hGhrelin(1-28)-NH₂; Example #95 (SEQ ID NO: 95)(isobutyryl-Gly¹)hGhrelin(1-28)-NH₂; Example #99 (SEQ ID NO: 95)(n-octanoyl-Gly¹)hGhrelin(1-28)-NH₂; Example #92 (SEQ ID NO: 1)Cys³(S(CH₂)₉CH₃)hGhrelin(1-28)-NH₂; Example #61 (SEQ ID NO: 3)(Lys⁵)hGhrelin(1-28)-NH₂ Example #42 (SEQ ID NO: 10)(Aib², Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 4)(Aib^(2,6), Ser³)hGhrelin(1-28)-NH₂ (SEQ ID NO: 8)(Aib², Ser³, 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 9)(Aib², Ser³, Thz⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 2)(Aib², Ser³, Cha⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 4)(Aib², Ser³, Abu⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 9)(Aib², Ser³, 4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 8)(Aib², Ser³, Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 9)(Aib², Ser³, Dhp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 11)(Aib^(2,8), Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 9)(Aib², Ser³, Pip⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 96)(Ac-Gly^(1,) Aib^(2,10), Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 12)(Aib^(2,10), Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 97)(n-butyryl-Gly¹, Aib², Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 97)(Ac-Gly¹, Aib², Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 9)(Aib², Ser³, Tic⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 98)(Ac-Gly¹, Aib², Ser³, Arg⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO: 16)(Ser³, Aib⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO: 14)(Ser³, Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 14)(Ser³, 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 14)(Ser³, 4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 8)(Aib², Ser³, 2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 14)(Ser³, 2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 15)(Ser³, 4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 9)(Aib², Ser³, Tic⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 99)(Aib², Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 99)(Aib^(2,6), Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 100)(A5c⁵, Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 101)(Aib², Thr³, 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 102)(Aib², Thr³, Thz⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 103)(Aib², Thr³, Cha⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 99)(Aib², Thr³, Abu⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 102)(Aib², Thr³, 4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 101)(Aib², Thr³, Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 102)(Aib², Thr³, Dhp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 11)(Aib^(2,8), Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 102)(Aib², Thr³, Pip⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 104)(Ac-Gly¹, Aib^(2,10), Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 106)(Aib^(2,10), Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 105)(n-butyryl-Gly¹, Aib², Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 105)(Ac-Gly¹, Aib², Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 102)(Aib², Thr³, Tic⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 90)(Ac-Gly¹, Aib², Thr³, Arg⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO: 107)(Thr³, Aib⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO: 108)(Thr³, Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 108)(Thr³, 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 108)(Thr³, 4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 101)(Aib², Thr³, 2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 108)(Thr³, 2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 109)(Thr³, 4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 102)(Aib², Thr³, Tic⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 110)(Ac-Gly¹, Glu³(NH-hexyl))hGhrelin(1-28)-NH₂; oror pharmaceutically acceptable salts thereof.

In one aspect, the invention provides a method of treatinggastrointestinal conditions such as gastroesophageal reflux disease,IBS, constipation, ileus, emesis, gastroparesis, and colonicpseudo-obstruction and the like, by administering a therapeuticallyeffective amount of a peptidyl ghrelin analog according to the followingformula (II):

R¹-A¹-A²-A³-A⁴-A⁵-R²

wherein:

A¹ is Aib, Apc or Inp;

A² is D-Bal, D-Bip, D-Bpa, D-Dip, D-1-Nal, D-2-Nal, D-Ser(Bzl), orD-Trp;

A³ is D-Bal, D-Bip, D-Bpa, D-Dip, D-1-Nal, D-2-Nal, D-Ser(Bzl), orD-Trp;

A⁴ is 2-Fua, Orn, 2-Pal, 3-Pal, 4-Pal, Pff, Phe, Pim, Taz, 2-Thi, 3-Thi,Thr(Bzl);

A⁵ is Apc, Dab, Dap, Lys, Orn, or deleted;

R¹ is hydrogen, (C₁₋₆)alkyl, (C₅₋₁₄)aryl, (C₁₋₆)alkyl(C₅₋₁₄)aryl,(C₃₋₈)cycloakyl, or (C₂₋₁₀)acyl; and

R² is OH or NH₂;

provided that when A⁵ is Dab, Dap, Lys, or Orn, then:

-   -   A² is D-Bip, D-Bpa, D-Dip or D-Bal; or    -   A³ is D-Bip, D-Bpa, D-Dip or D-Bal; or    -   A⁴ is 2-Thi, 3-Thi, Taz, 2-Fua, 2-Pal, 3-Pal, 4-Pal, Orn,        Thr(Bzl), or Pff;        when A⁵ is deleted, then:    -   A³ is D-Bip, D-Bpa, or D-Dip; or    -   A⁴ is 2-Fua, Pff, Taz, or Thr(Bzl); or    -   A¹ is Apc when        -   A² is D-Bip, D-Bpa, D-Dip or D-Bal; or        -   A³ is D-Bip, D-Bpa, D-Dip or D-Bal; or        -   A⁴ is 2-Thi, 3-Thi, Orn, 2-Pal, 3-Pal or 4-Pal;            or a pharmaceutically acceptable salt thereof.

In yet another aspect, the invention provides a preferred compound offormula (II), wherein:

A¹ is Aib, Apc or H-Inp;

A² is D-Bal, D-Bip, D-Bpa, D-Dip, D-1-Nal, D-2-Nal, D-Ser(Bzl), orD-Trp;

A³ is D-Bal, D-Bpa, D-Dip, D-1-Nal, D-2-Nal, or D-Trp;

A⁴ is Orn, 3-Pal, 4-Pal, Pff, Phe, Pim, Taz, 2-Thi, or Thr(Bzl); and

A⁵ is Apc, Lys, or deleted;

or a pharmaceutically acceptable salt thereof.

In yet another aspect of the immediately foregoing group of compounds,the invention provides a preferred compound of formula (II), wherein:

A¹ is Apc or H-Inp;

A² is D-Bal, D-Bip, D-1-Nal, or D-2-Nal;

A³ is D-Bal, D-1-Nal, D-2-Nal, or D-Trp;

A⁴ is 3-Pal, 4-Pal, Pff, Phe, Pim, Taz, 2-Thi, or Thr(Bzl); and

or a pharmaceutically acceptable salt thereof.

In yet another aspect, the invention provides a preferred group ofcompounds according to formula (I), where the compound is:

(SEQ ID NO: 111) Inp-D-2-Nal-D-Trp-Phe-Lys-NH₂ Example 2(SEQ ID NO: 112) H-Inp-D-1-Nal-D-Trp-3-Pal-Lys-NH₂; Example #50(SEQ ID NO: 113) H-Inp-D-2-Nal-D-Trp-4-Pal-Lys-NH₂; (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-Orn-Lys-NH₂; Example #116 (SEQ ID NO: 111)H-Inp-D-Bip-D-Trp-Phe-Lys-NH₂; Example #66 (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-Thr(Bzl)-Lys-NH₂; (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-Pff-Lys-NH₂; Example #100 (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-2-Thi-Lys-NH₂; Example #15 (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-Taz-Lys-NH₂; Example #37 (SEQ ID NO: 111)H-Inp-D-Dip-D-Trp-Phe-Lys-NH₂; Example #105 (SEQ ID NO: 111)H-Inp-D-Bpa-D-Trp-Phe-Lys-NH₂; Example #109 (SEQ ID NO: 114)H-Inp-D-2-Nal-D-Bpa-Phe-Lys-NH₂; Example #118 (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-3-Pal-NH₂; Example #93 (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-4-Pal-NH₂; Example #112 (SEQ ID NO: 116)H-Inp-D-1-Nal-D-Trp-3-Pal-NH₂; Example #97 (SEQ ID NO: 117)H-Inp-D-Bip-D-Trp-Phe-NH₂; Example #98 (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-Thr(Bzl)-NH₂; Example #87 (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-Pff-NH₂; Example #103 (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-2-Thi-NH₂; Example #84 (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-Taz-NH₂; Example #90 (SEQ ID NO: 117)H-Inp-D-Dip-D-Trp-Phe-NH₂; Example #111 (SEQ ID NO: 118)H-Inp-D-2-Nal-D-Dip-Phe-NH₂; Example #110 (SEQ ID NO: 119)H-Inp-D-Bal-D-Trp-Phe-NH₂; Example #78 (SEQ ID NO: 118)H-Inp-D-2-Nal-D-Bal-Phe-NH₂; Example #101 (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-3-Pal-Lys-NH₂; Example #71 (SEQ ID NO: 120)H-Inp-D-Trp-D-2-Nal(Ψ)-Pim; Example #115 (SEQ ID NO: 121)H-Inp-D-Bal-D-Trp-2-Thi-Lys-NH₂; Example #12 (SEQ ID NO: 111)H-Inp-D-Bal-D-Trp-Phe-Lys-NH₂; Example #5 (SEQ ID NO: 112)H-Inp-D-1-Nal-D-Trp-2-Thi-Lys-NH₂; Example #3 (SEQ ID NO: 122)H-Inp-D-2-Nal-D-Trp-Phe-Apc-NH₂; Example #28 (SEQ ID NO: 122)H-Inp-D-1-Nal-D-Trp-Phe-Apc-NH₂; Example #6 (SEQ ID NO: 122)H-Inp-D-Bal-D-Trp-Phe-Apc-NH₂; Example #19 (SEQ ID NO: 123)H-Apc-D-2-Nal-D-Trp-Phe-Lys-NH₂; Example #11 (SEQ ID NO: 124)H-Apc-D-1-Nal-D-Trp-2-Thi-Lys-NH₂; Example #1 (SEQ ID NO: 116)H-Inp-D-1-Nal-D-Trp-2-Thi-NH₂; Example #39 (SEQ ID NO: 125)H-Apc-D-1-Nal-D-Trp-Phe-NH₂; Example #31 (SEQ ID NO: 126)H-Inp-D-2-Nal-D-Trp(Ψ)-Pim; Example #113 (SEQ ID NO: 126)H-Inp-D-1-Nal-D-Trp(Ψ)-Pim; Example #107 (SEQ ID NO: 126)H-Inp-D-Bal-D-Trp(Ψ)-Pim; Example #106 (SEQ ID NO: 127)H-Aib-D-Ser(Bzl)-D-Trp(Ψ)-Pim; Example #119 (SEQ ID NO: 112)H-Inp-D-1-Nal-D-Trp-Taz-Lys-NH₂; Example #57 (SEQ ID NO: 121)H-Inp-D-Bal-D-Trp-Taz-Lys-NH₂; Example #23 (SEQ ID NO: 124)H-Apc-D-1-Nal-D-Trp-Taz-Lys-NH₂; Example #14 (SEQ ID NO: 128)H-Apc-D-Bal-D-Trp-Taz-Lys-NH₂; Example #20 (SEQ ID NO: 128)H-Apc-D-Bal-D-Trp-2-Thi-Lys-NH₂; Example #7 (SEQ ID NO: 123)H-Apc-D-Bal-D-Trp-Phe-Lys-NH₂; Example #4 (SEQ ID NO: 129)H-Apc-D-1-Nal-D-Trp-Phe-Apc-NH₂; Example #18 (SEQ ID NO: 130)H-Apc-D-Bal-D-Trp-Phe-Apc-NH₂; Example #33 (SEQ ID NO: 129)H-Apc-D-1-Nal-D-1-Nal-Phe-Apc-NH₂; Example #74 (SEQ ID NO: 129)H-Apc-D-1-Nal-D-2-Nal-Phe-Apc-NH₂; Example #73 (SEQ ID NO: 131)H-Apc-D-1-Nal-D-1-Nal-Phe-Lys-NH₂; Example #64 (SEQ ID NO: 130)H-Apc-D-Bal-D-1-Nal-Phe-Apc-NH₂; Example #83 (SEQ ID NO: 130)H-Apc-D-Bal-D-2-Nal-Phe-Apc-NH₂; Example #69 (SEQ ID NO: 132)H-Apc-D-Bal-D-1-Nal-Phe-Lys-NH₂; (SEQ ID NO: 132)H-Apc-D-Bal-D-2-Nal-Phe-Lys-NH₂; Example #30 (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-2-Thi-NH₂; Example #34 (SEQ ID NO: 125)H-Apc-D-Bal-D-Trp-Phe-NH₂; Example #41 (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-Taz-NH₂; Example #67 (SEQ ID NO: 144)H-Apc-D-Bal-D-Trp-2-Thi-NH₂; Example #47 (SEQ ID NO: 144)H-Apc-D-Bal-D-Trp-Taz-NH₂; Example #72 (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-2-Thi-NH₂; Example #45 (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-Taz-NH₂; Example #77 (SEQ ID NO: 135)H-Inp-D-1-Nal-D-Trp-Taz-Apc-NH₂; Example #60 (SEQ ID NO: 135)H-Inp-D-Bal-D-Trp-Taz-Apc-NH₂; Example #38 (SEQ ID NO: 136)H-Apc-D-1-Nal-D-Trp-Taz-Apc-NH₂; Example #46 (SEQ ID NO: 136)H-Apc-D-Bal-D-Trp-Taz-Apc-NH₂; Example #58 (SEQ ID NO: 137)H-Apc-D-1-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 124)H-Apc-D-1-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-2-Pal-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-3-Pal-NH₂; (SEQ ID NO: 137)H-Apc-D-1-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 124)H-Apc-D-1-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-3-Thi-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-4-Pal-NH₂; (SEQ ID NO: 137)H-Apc-D-1-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO: 124)H-Apc-D-1-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-Pff-NH₂; (SEQ ID NO: 138)H-Apc-D-2-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 139)H-Apc-D-2-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-2-Pal-NH₂; (SEQ ID NO: 138)H-Apc-D-2-Nal-D-Trp-2-Thi-Apc-NH₂; (SEQ ID NO: 139)H-Apc-D-2-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-3-Pal-NH₂; (SEQ ID NO: 138)H-Apc-D-2-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 139)H-Apc-D-2-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-3-Thi-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-4-Pal-NH₂; (SEQ ID NO: 138)H-Apc-D-2-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO: 139)H-Apc-D-2-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-Pff-NH₂; (SEQ ID NO: 136)H-Apc-D-2-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO: 139)H-Apc-D-2-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO: 140)H-Apc-D-Bal-D-Bal-2-Fua-Apc-NH₂; (SEQ ID NO: 141)H-Apc-D-Bal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-2-Fua-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-2-Pal-NH₂; (SEQ ID NO: 140)H-Apc-D-Bal-D-Bal-2-Thi-Apc-NH₂; (SEQ ID NO: 141)H-Apc-D-Bal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-2-Thi-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-3-Pal-NH₂; (SEQ ID NO: 140)H-Apc-D-Bal-D-Bal-3-Thi-Apc-NH₂; (SEQ ID NO: 141)H-Apc-D-Bal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-3-Thi-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-4-Pal-NH₂; (SEQ ID NO: 140)H-Apc-D-Bal-D-Bal-Pff-Apc-NH₂; (SEQ ID NO: 141)H-Apc-D-Bal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-Pff-NH₂; (SEQ ID NO: 130)H-Apc-D-Bal-D-Bal-Phe-Apc-NH₂; (SEQ ID NO: 132)H-Apc-D-Bal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-Phe-NH₂; (SEQ ID NO: 140)H-Apc-D-Bal-D-Bal-Taz-Apc-NH₂; (SEQ ID NO: 141)H-Apc-D-Bal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-Taz-NH₂; (SEQ ID NO: 143)H-Apc-D-Bal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 128)H-Apc-D-Bal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 144)H-Apc-D-Bal-D-Trp-2-Fua-NH₂; (SEQ ID NO: 144)H-Apc-D-Bal-D-Trp-2-Pal-NH₂; (SEQ ID NO: 144)H-Apc-D-Bal-D-Trp-3-Pal-NH₂; (SEQ ID NO: 143)H-Apc-D-Bal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 128)H-Apc-D-Bal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 144)H-Apc-D-Bal-D-Trp-3-Thi-NH₂; (SEQ ID NO: 144)H-Apc-D-Bal-D-Trp-4-Pal-NH₂; (SEQ ID NO: 143)H-Apc-D-Bal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO: 128)H-Apc-D-Bal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 144)H-Apc-D-Bal-D-Trp-Pff-NH₂; (SEQ ID NO: 145)H-Inp-D-1-Nal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO: 146)H-Inp-D-1-Nal-D-Bal-2-Fua-NH₂; (SEQ ID NO: 145)H-Inp-D-1-Nal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO: 145)H-Inp-D-1-Nal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO: 145)H-Inp-D-1-Nal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO: 146)H-Inp-D-1-Nal-D-Bal-Pff-NH₂; (SEQ ID NO: 145)H-Inp-D-1-Nal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO: 145)H-Inp-D-1-Nal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO: 146)H-Inp-D-1-Nal-D-Bal-Taz-NH₂; (SEQ ID NO: 147)H-Inp-D-1-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 112)H-Inp-D-1-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 116)H-Inp-D-1-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO: 147)H-Inp-D-1-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 112)H-Inp-D-1-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 147)H-Inp-D-1-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO: 112)H-Inp-D-1-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 116)H-Inp-D-1-Nal-D-Trp-Pff-NH₂; (SEQ ID NO: 116)H-Inp-D-1-Nal-D-Trp-Taz-NH₂; (SEQ ID NO: 148)H-Inp-D-2-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO: 148)H-Inp-D-2-Nal-D-Trp-2-Thi-Apc-NH₂; (SEQ ID NO: 148)H-Inp-D-2-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-3-Thi-NH₂; (SEQ ID NO: 148)H-Inp-D-2-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-Pff-NH₂; (SEQ ID NO: 135)H-Inp-D-2-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-Taz-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO: 150)H-Inp-D-Bal-D-Bal-2-Fua-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO: 150)H-Inp-D-Bal-D-Bal-Pff-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO: 150)H-Inp-D-Bal-D-Bal-Taz-NH₂; (SEQ ID NO: 151)H-Inp-D-Bal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 121)H-Inp-D-Bal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 152)H-Inp-D-Bal-D-Trp-2-Fua-NH₂; (SEQ ID NO: 151)H-Inp-D-Bal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 121)H-Inp-D-Bal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 151)H-Inp-D-Bal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO: 121)H-Inp-D-Bal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 152)H-Inp-D-Bal-D-Trp-Pff-NH₂; (SEQ ID NO: 152) H-Inp-D-Bal-D-Trp-Taz-NH₂;(SEQ ID NO: 153) H-Inp-D-Bip-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO: 154)H-Inp-D-Bip-D-Bal-2-Fua-NH₂; (SEQ ID NO: 153)H-Inp-D-Bip-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO: 153)H-Inp-D-Bip-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO: 153)H-Inp-D-Bip-D-Bal-Pff-Lys-NH₂; (SEQ ID NO: 154)H-Inp-D-Bip-D-Bal-Pff-NH₂; or (SEQ ID NO: 153)H-Inp-D-Bip-D-Bal-Taz-Lys-NH₂; (SEQ ID NO: 154)H-Inp-D-Bip-D-Bal-Taz-NH₂; (SEQ ID NO: 155)H-Inp-D-Bip-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 156)H-Inp-D-Bip-D-Trp-2-Fua-NH₂; (SEQ ID NO: 155)H-Inp-D-Bip-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO: 155)H-Inp-D-Bip-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 155)H-Inp-D-Bip-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 156)H-Inp-D-Bip-D-Trp-Pff-NH₂; (SEQ ID NO: 155)H-Inp-D-Bip-D-Trp-Taz-Lys-NH₂; or (SEQ ID NO: 156)H-Inp-D-Bip-D-Trp-Taz-NH₂; (SEQ ID NO: 112)H-Inp-D-1-Nal-D-Trp-3-Pal-Lys-NH₂; (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-4-Pal-Lys-NH₂; Example #91 (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-Orn-Lys-NH₂; (SEQ ID NO: 111)H-Inp-D-Bip-D-Trp-Phe-Lys-NH₂; (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-Thr(Bzl)-Lys-NH₂; Example #70 (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO: 111)H-Inp-D-Dip-D-Trp-Phe-Lys-NH₂; (SEQ ID NO: 111)H-Inp-D-Bpa-D-Trp-Phe-Lys-NH₂; (SEQ ID NO: 114)H-Inp-D-2-Nal-D-Bpa-Phe-Lys-NH₂; (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-Thr(Bzl)-NH₂; (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-Pff-NH₂; (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-Taz-NH₂; (SEQ ID NO: 118)H-Inp-D-2-Nal-D-Dip-Phe-NH₂; (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-3-Pal-Lys-NH₂; (SEQ ID NO: 120)H-Inp-D-Trp-D-2-Nal(Ψ)-Pim; (SEQ ID NO: 121)H-Inp-D-Bal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO: 111)H-Inp-D-Bal-D-Trp-Phe-Lys-NH₂; (SEQ ID NO: 112)H-Inp-D-1-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO: 122)H-Inp-D-2-Nal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO: 122)H-Inp-D-1-Nal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO: 122)H-Inp-D-Bal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO: 123)H-Apc-D-2-Nal-D-Trp-Phe-Lys-NH₂; (SEQ ID NO: 124)H-Apc-D-1-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO: 126)H-Inp-D-2-Nal-D-Trp(Ψ)-Pim; (SEQ ID NO: 126) H-Inp-D-1-Nal-D-Trp(Ψ)-Pim;(SEQ ID NO: 126) H-Inp-D-Bal-D-Trp(Ψ)-Pim; (SEQ ID NO: 127)H-Aib-D-Ser(Bzl)-D-Trp(Ψ)-Pim; (SEQ ID NO: 112)H-Inp-D-1-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO: 121)H-Inp-D-Bal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO: 124)H-Apc-D-1-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO: 128)H-Apc-D-Bal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO: 128)H-Apc-D-Bal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO: 123)H-Apc-D-Bal-D-Trp-Phe-Lys-NH₂; (SEQ ID NO: 129)H-Apc-D-1-Nal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO: 130)H-Apc-D-Bal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO: 129)H-Apc-D-1-Nal-D-1-Nal-Phe-Apc-NH₂; (SEQ ID NO: 129)H-Apc-D-1-Nal-D-2-Nal-Phe-Apc-NH₂; (SEQ ID NO: 131)H-Apc-D-1-Nal-D-1-Nal-Phe-Lys-NH₂; (SEQ ID NO: 130)H-Apc-D-Bal-D-1-Nal-Phe-Apc-NH₂; (SEQ ID NO: 130)H-Apc-D-Bal-D-2-Nal-Phe-Apc-NH₂; (SEQ ID NO: 132)H-Apc-D-Bal-D-1-Nal-Phe-Lys-NH₂; (SEQ ID NO: 132)H-Apc-D-Bal-D-2-Nal-Phe-Lys-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-2-Thi-NH₂; (SEQ ID NO: 157)H-Apc-D-Bal-D-Trp-Phe-NH₂; (SEQ ID NO: 133) H-Apc-D-1-Nal-D-Trp-Taz-NH₂;(SEQ ID NO: 157) H-Apc-D-Bal-D-Trp-2-Thi-NH₂; (SEQ ID NO: 157)H-Apc-D-Bal-D-Trp-Taz-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-2-Thi-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-Taz-NH₂; (SEQ ID NO: 135)H-Inp-D-1-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO: 135)H-Inp-D-Bal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO: 136)H-Apc-D-1-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO: 136)H-Apc-D-Bal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO: 113)H-Inp-D-2-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 121)H-Inp-D-Bal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 121)H-Inp-D-Bal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 121)H-Inp-D-Bal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 151)H-Inp-D-Bal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 151)H-Inp-D-Bal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 151)H-Inp-D-Bal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO: 128)H-Apc-D-Bal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 128)H-Apc-D-Bal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 128)H-Apc-D-Bal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO: 149)H-Inp-D-Bal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO: 132)H-Apc-D-Bal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO: 141)H-Apc-D-Bal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO: 141)H-Apc-D-Bal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO: 141)H-Apc-D-Bal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO: 141)H-Apc-D-Bal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO: 141)H-Apc-D-Bal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO: 112)H-Inp-D-1-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 112)H-Inp-D-1-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 112)H-Inp-D-1-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 158)H-Inp-D-1-Nal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO: 158)H-Inp-D-1-Nal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO: 158)H-Inp-D-1-Nal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO: 158)H-Inp-D-1-Nal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO: 158)H-Inp-D-1-Nal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO: 158)H-Inp-D-1-Nal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO: 159)H-Inp-D-2-Nal-D-Trp-2-Thi-Apc-NH₂; (SEQ ID NO: 159)H-Inp-D-2-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 135)H-Inp-D-2-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO: 159)H-Inp-D-2-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 159)H-Inp-D-2-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO: 160)H-Inp-D-1-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 160)H-Inp-D-1-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 160)H-Inp-D-1-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO: 124)H-Apc-D-1-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 124)H-Apc-D-1-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 124)H-Apc-D-1-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 139)H-Apc-D-2-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO: 139)H-Apc-D-2-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 139)H-Apc-D-2-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO: 139)H-Apc-D-2-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 139)H-Apc-D-2-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 155)H-Inp-D-Bip-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO: 155)H-Inp-D-Bip-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO: 155)H-Inp-D-Bip-D-Trp-Taz-Lys-NH₂; (SEQ ID NO: 155)H-Inp-D-Bip-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO: 155)H-Inp-D-Bip-D-Trp-Pff-Lys-NH₂; (SEQ ID NO: 153)H-Inp-D-Bip-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO: 153)H-Inp-D-Bip-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO: 153)H-Inp-D-Bip-D-Bal-Taz-Lys-NH₂; (SEQ ID NO: 153)H-Inp-D-Bip-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO: 153)H-Inp-D-Bip-D-Bal-Pff-Lys-NH₂; (SEQ ID NO: 143)H-Apc-D-Bal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 143)H-Apc-D-Bal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 143)H-Apc-D-Bal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO: 130)H-Apc-D-Bal-D-Bal-Phe-Apc-NH₂; (SEQ ID NO: 140)H-Apc-D-Bal-D-Bal-2-Thi-Apc-NH₂; (SEQ ID NO: 140)H-Apc-D-Bal-D-Bal-3-Thi-Apc-NH₂; (SEQ ID NO: 140)H-Apc-D-Bal-D-Bal-Taz-Apc-NH₂; (SEQ ID NO: 140)H-Apc-D-Bal-D-Bal-2-Fua-Apc-NH₂; (SEQ ID NO: 140)H-Apc-D-Bal-D-Bal-Pff-Apc-NH₂; (SEQ ID NO: 137)H-Apc-D-1-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 137)H-Apc-D-1-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 137)H-Apc-D-1-Nal-D-Trp-Pff-Apc-NH₂;  (SEQ ID NO: 138)H-Apc-D-2-Nal-D-Trp-2-Thi-Apc-NH₂; (SEQ ID NO: 138)H-Apc-D-2-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO: 136)H-Apc-D-2-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO: 138)H-Apc-D-2-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO: 138)H-Apc-D-2-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO: 152)H-Inp-D-Bal-D-Trp-Taz-NH₂; (SEQ ID NO: 152) H-Inp-D-Bal-D-Trp-2-Fua-NH₂;(SEQ ID NO: 152) H-Inp-D-Bal-D-Trp-Pff-NH₂; (SEQ ID NO: 157)H-Apc-D-Bal-D-Trp-3-Thi-NH₂; (SEQ ID NO: 157)H-Apc-D-Bal-D-Trp-2-Fua-NH₂; (SEQ ID NO: 157) H-Apc-D-Bal-D-Trp-Pff-NH₂;(SEQ ID NO: 157) H-Apc-D-Bal-D-Trp-4-Pal-NH₂; (SEQ ID NO: 157)H-Apc-D-Bal-D-Trp-3-Pal-NH₂; (SEQ ID NO: 157)H-Apc-D-Bal-D-Trp-2-Pal-NH₂; (SEQ ID NO: 150) H-Inp-D-Bal-D-Bal-Taz-NH₂;(SEQ ID NO: 150) H-Inp-D-Bal-D-Bal-2-Fua-NH₂; (SEQ ID NO: 150)H-Inp-D-Bal-D-Bal-Pff-NH₂; (SEQ ID NO: 142) H-Apc-D-Bal-D-Bal-Phe-NH₂;(SEQ ID NO: 142) H-Apc-D-Bal-D-Bal-2-Thi-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-3-Thi-NH₂; (SEQ ID NO: 142) H-Apc-D-Bal-D-Bal-Taz-NH₂;(SEQ ID NO: 142) H-Apc-D-Bal-D-Bal-2-Fua-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-Pff-NH₂; (SEQ ID NO: 142) H-Apc-D-Bal-D-Bal-4-Pal-NH₂;(SEQ ID NO: 142) H-Apc-D-Bal-D-Bal-3-Pal-NH₂; (SEQ ID NO: 142)H-Apc-D-Bal-D-Bal-2-Pal-NH₂; (SEQ ID NO: 116)H-Inp-D-1-Nal-D-Trp-Taz-NH₂; (SEQ ID NO: 116)H-Inp-D-1-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO: 116)H-Inp-D-1-Nal-D-Trp-Pff-NH₂; (SEQ ID NO: 161)H-Inp-D-1-Nal-D-Bal-Taz-NH₂; (SEQ ID NO: 161)H-Inp-D-1-Nal-D-Bal-2-Fua-NH₂; (SEQ ID NO: 161)H-Inp-D-1-Nal-D-Bal-Pff-NH₂; (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-Taz-NH₂; (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO: 115)H-Inp-D-2-Nal-D-Trp-Pff-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-3-Thi-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-Pff-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-4-Pal-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-3-Pal-NH₂; (SEQ ID NO: 133)H-Apc-D-1-Nal-D-Trp-2-Pal-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-3-Thi-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-Pff-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-4-Pal-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-3-Pal-NH₂; (SEQ ID NO: 134)H-Apc-D-2-Nal-D-Trp-2-Pal-NH₂; (SEQ ID NO: 156)H-Inp-D-Bip-D-Trp-Taz-NH₂; (SEQ ID NO: 156) H-Inp-D-Bip-D-Trp-2-Fua-NH₂;(SEQ ID NO: 156) H-Inp-D-Bip-D-Trp-Pff-NH₂; (SEQ ID NO: 154)H-Inp-D-Bip-D-Bal-Taz-NH₂; (SEQ ID NO: 154) H-Inp-D-Bip-D-Bal-2-Fua-NH₂;or (SEQ ID NO: 154) H-Inp-D-Bip-D-Bal-Pff-NH₂; (SEQ ID NO: 147)H-Inp-D-1-Nal-D-Trp-2-Thi-Apc-NH₂; Example #24 (SEQ ID NO: 151)H-Inp-D-Bal-D-Trp-2-Thi-Apc-NH₂; Example #9 (SEQ ID NO: 137)H-Apc-D-1-Nal-D-Trp-2-Thi-Apc-NH₂; Example #17 (SEQ ID NO: 143)H-Apc-D-Bal-D-Trp-2-Thi-Apc-NH₂; Example #22 or (SEQ ID NO: 131)H-Apc-D-1-Nal-D-Trp-Phe-Lys-NH₂ Example #13or a pharmaceutically acceptable salts thereof.

In yet another aspect, the invention provides a method of treatinggastrointestinal conditions such as gastroesophageal reflux disease,IBS, constipation, ileus, emesis, gastroparesis, and colonicpseudo-obstruction and the like, by administering a therapeuticallyeffective amount of a peptidyl ghrelin analog according to the followingformula (III):

(R²R³)-A¹-A²-A³-A⁴-A⁵-A⁶-A⁷-A⁸-A⁹-A¹⁰-A¹¹-A¹²-A¹³-A¹⁴-A¹⁵-A¹⁶-A¹⁷-A¹⁸-A¹⁹-A²⁰-A²¹-A²²-A²³-A²⁴-A²⁵-A²⁶-A²⁷-A²⁸-R¹

wherein:

A¹ is Gly, Aib, Ala, β-Ala, Acc or Gly(myristyl);

A² is Ser, Aib, Ala, Acc, Abu, Act, Ava, Thr or Val;

A³ is Ser, Ser(C(O)—R⁴), Asp(O—R⁸), Asp(NH—R⁹), Cys(S—R¹⁴),Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹), Glu(O—R⁶), Glu(NH—R⁷), Thr(C(O)—R⁵) orHN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O);

A⁴ is Phe, Acc, Aic, Cha, 2-Fua, 1-Nal, 2-Nal, 2-Pal, 3-Pal, 4-Pal,hPhe, (X¹,X²,X³,X⁴,X⁵)Phe, Taz, 2-Thi, 3-Thi, Trp or Tyr;

A⁵ is Leu, Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle orVal;

A⁶ is Ser, Abu, Acc, Act, Aib, Ala, Gly, Thr or Val;

A⁷ is Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz or Tic;

A⁸ is Glu, Acc, Aib, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn orHN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O);

A⁹ is His, Apc, Aib, Acc, 2-Fua, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thior (X¹, X², X³, X⁴, X⁵-)Phe;

A¹⁰ is Gln, Acc, Aib, Asn, Asp or Glu;

A¹¹ is Arg, Apc, hArg, Dab, Dap, Lys, Orn orHN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O);

A¹² is Val, Abu, Acc, Aib, Ala, Cha, Nva, Gly, Ile, Leu, Nle, Tle orCha;

A¹³ is Gln, Acc, Aib, Asn, Asp or Glu;

A¹⁴ is Gln, Acc, Aib, Asn, Asp or Glu;

A¹⁵ is Arg, hArg, Acc, Aib, Apc, Dab, Dap, Lys, Orn, Ser(C(O)—R⁴),Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸), Asp(NH—R⁹),Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹), HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O),Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶) or hCys(R¹⁷);

A¹⁶ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, Ser(C(O)—R⁴),Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸), Asp(NH—R⁹),Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹), HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O),Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶), hCys(R¹⁷) or deleted;

A¹⁷ is Glu, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn, Ser(C(O)—R⁴),Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸), Asp(NH—R⁹),Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹), HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O),Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶), hCys(R¹⁷), Lys(biotinyl) or deleted;

A¹⁸ is Ser, Abu, Acc, Act, Aib, Ala, Thr, Val, Ser(C(O)—R⁴),Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸), Asp(NH—R⁹),Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹), HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O),Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶), hCys(R¹⁷) or deleted;

A¹⁹ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, Ser(C(O)—R⁴),Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸), Asp(NH—R⁹),Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹), HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O),Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶), hCys(R¹⁷) or deleted;

A²⁰ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn, Ser(C(O)—R⁴),Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸), Asp(NH—R⁹),Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹), HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O),Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶), hCys(R¹⁷) or deleted;

A²¹ is Pro, Dhp, Dmt, Inc, 3-Hyp, 4-Hyp, Ktp, Oic, Pip, Thz, Tic ordeleted;

A²² is Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic ordeleted;

A²³ is Abu, Acc, Act, Aib, Ala, Apc, Gly, Nva, Val or deleted;

A²⁴ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O) or deleted;

A²⁵ is Leu, Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle, Valor deleted;

A²⁶ is Gln, Aib, Asn, Asp, Glu or deleted; A²⁷ is Pro, Dhp, Dmt, 3-Hyp,4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic or deleted;

A²⁸ is Acc, Aib, Apc, Arg, hArg, Dab, Dap, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O) or deleted;

R¹ is —OH, —NH₂, —(C₁-C₃₀)alkoxy or NH—X⁶—CH₂—Z⁰, wherein X⁶ is a(C₁-C₁₂)alkyl, (C₂-C₁₂)alkenyl and Z⁰ is —H, —OH, —CO₂H or —C(O)—NH₂;

R² and R³ is, independently for each occurrence thereof, selected fromthe group consisting of H, (C₁-C₃₀)alkyl, (C₁-C₃₀)heteroalkyl,(C₁-C₃₀)acyl, (C₂-C₃₀)alkenyl, (C₂-C₃₀)alkynyl, aryl(C₁-C₃₀)alkyl,aryl(C₁-C₃₀)acyl, substituted (C₁-C₃₀)alkyl, substituted(C₁-C₃₀)heteroalkyl, substituted (C₂-C₃₀)acyl, substituted(C₂-C₃₀)alkenyl, substituted aryl(C₁-C₃₀)alkyl and substitutedaryl(C₁-C₃₀)acyl;

R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is,independently for each occurrence thereof, selected from the groupconsisting of (C₁-C₄₀)alkyl, (C₂-C₄₀)alkenyl, substituted (C₁-C₄₀)alkyl, substituted (C₂-C₄₀) alkenyl, alkylaryl, substituted alklyaryl,aryl and substituted aryl;

R¹² and R⁴³ is, independently for each occurrence thereof, selected fromthe group consisting of H, (C₁-C₄₀)alkyl, (C₁-C₄₀)acyl,(C₁-C₃₀)alkylsulfonyl, biotinyl and —C(NH)—NH₂,

X¹, X², X³, X⁴, and X⁵ is, independently for each occurrence thereof,selected from the group consisting of H, F, Cl, Br, I, (C₁₋₁₀)alkyl,substituted (C₁₋₁₀)alkyl, aryl, substituted aryl, OH, NH₂, NO₂ and CN;and

n is, independently for each occurrence thereof, 1, 2, 3, 4 or 5;

provided that:

(I). when R² is (C₁-C₃₀)acyl, aryl(C₁-C₃₀)acyl, substituted(C₂-C₃₀)acyl, or substituted aryl(C₁-C₃₀)acyl, R³ is H, (C₁-C₃₀)alkyl,(C₁-C₃₀)heteroalkyl, (C₂-C₃₀)alkenyl, aryl(C₁-C₃₀)alkyl, substituted(C₁-C₃₀)alkyl, substituted (C₁-C₃₀)heteroalkyl, substituted(C₂-C₃₀)alkenyl or substituted aryl(C₁-C₃₀)alkyl;

(II). when R¹² is (C₁-C₄₀)acyl, (C₁-C₃₀)alkylsulfonyl, biotinyl or—C(NH)—NH₂, then R¹³ is H or (C₁-C₄₀)alkyl;

(III). at least one of A¹⁵, A¹⁶, A¹⁷, A¹⁸, A¹⁹ or A²⁰ must be selectedfrom the group consisting of Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶),Glu(NH—R⁷), Asp(O—R⁸), Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹),HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶) andhCys(R¹⁷); and

(IV). when any of the group consisting of A¹⁵, A¹⁶, A¹⁷, A¹⁸, A¹⁹ andA²⁰ is HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), then R¹² must be biotinyl;

or a pharmaceutically acceptable salt thereof.

In yet another aspect, the invention provides a preferred group ofcompounds according to formula (III), where in:

each of R² and R³ is, independently for each occurrence thereof,selected from the group consisting of H, acyl, n-butyryl, isobutyryl andn-octanoyl;

R⁴ is heptyl;

R⁶ is hexyl;

R⁷ is hexyl;

R¹⁰ is octyl;

R¹¹ is heptyl; and

provided that when Acc is substituted for one of the naturally-occurringresidues, it is, independently for each occurrence, A3c, A4c, A5c orA6c; or pharmaceutically acceptable salts thereof.

In yet another aspect, the invention provides a preferred group ofcompounds according to formula (III), where the compound is:

(SEQ ID NO: 162) (Ser(n-octanoyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 163)(Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 164)(Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂; (SEQ ID NO: 165)(Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 166)(Aib², Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 167)(Aib², Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂; (SEQ ID NO: 168)(Aib^(2,8), Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 169)(Aib^(2,8), Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂; (SEQ ID NO: 170)(Aib^(2,10), Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO: 171)(Aib^(2,10), Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂; (SEQ ID NO: 172)(Ser(n-octanoyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 173)(Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 174)(Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂; (SEQ ID NO: 175)(Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 176)(Aib², Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 177)(Aib², Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂; (SEQ ID NO: 178)(Aib^(2,8), Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 179)(Aib^(2,8), Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂; (SEQ ID NO: 180)(Aib^(2,10), Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO: 181)(Aib^(2,10), Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂; (SEQ ID NO: 182)(Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 183)(Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 184)(Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂; (SEQ ID NO: 185)(Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 186)(Dap(octanesulfonyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 187)(Dap(octanesulfonyl)^(3,17))hGhrelin(1-28)-NH₂; (SEQ ID NO: 188)(Dap(octanesulfonyl)³, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 189)(Dap(octanesulfonyl)³, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 190)(Glu(NH-hexyl)³, Dap(octanesulfonyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 191) (Cys(S-(CH₂)₉CH₃)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 192) (Cys(S-(CH₂)₉CH₃)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 193) (Glu(NH-hexyl)³, Cys(S-(CH²)⁹CH³)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 194) (Cys(S-(CH₂)₉CH₃)³, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 195)(Cys(S-(CH₂)₉CH₃)³, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 196) (Aib², Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 197) (Aib², Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 198) (Aib², Thz⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 198) (Aib², 4-Hyp⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 198) (Aib², Dhp⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 198) (Aib², Pip⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 198) (Aib², Tic⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 199) (Aib², Glu(NH-hexyl)^(3,17), Thz⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 200) (Aib², Glu(NH-hexyl)^(3,17), 4-Hyp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 200) (Aib², Glu(NH-hexyl)^(3,17), Dhp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 200) (Aib², Glu(NH-hexyl)^(3,17), Pip⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 200) (Aib², Glu(NH-hexyl)^(3,17), Tic⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 201) (Aib^(2,8), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 202)(Aib^(2,8), Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂; Example #16(SEQ ID NO: 203) (Aib², 3-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 203) (Aib², 4-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 203) (Aib², Taz⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 203) (Aib², 2-Thi⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 204) (Aib², Glu(NH-hexyl)^(3,17), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 204) (Aib², Glu(NH-hexyl)^(3,17), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 204) (Aib², Glu(NH-hexyl)^(3,17), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 204) (Aib², Glu(NH-hexyl)^(3,17), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 205) (Aib^(2,10), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 206) (Aib^(2,10), Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 207) (Aib⁸, Glu(NH-hexyl)^(3,7))hGhrelin(1-28)-NH₂;(SEQ ID NO: 208) (Taz⁹, Glu(NH-hexyl)^(3,7))hGhrelin(1-28)-NH₂;(SEQ ID NO: 208) (3-PaP, Glu(NH-hexyl)^(3,7))hGhrelin(1-28)-NH₂;(SEQ ID NO: 208) (4-PaP, Glu(NH-hexyl)^(3,7))hGhrelin(1-28)-NH₂;(SEQ ID NO: 208) (2-Thi9, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 209) (Glu(NH-hexyl)^(3,17), Aib⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO: 210) (Glu(NH-hexyl)^(3,17), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 210) (Glu(NH-hexyl)^(3,17), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 210) (Glu(NH-hexyl)^(3,17), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 210) (Glu(NH-hexyl)^(3,17), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 211) (Aib^(1,2,10), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 212) (Aib^(1,2,10), Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 196) (A5c², Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 197) (A5c², Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 184) (Glu(1-heptanol)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 213) (Asp(1-heptanol)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 184) (Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 213) (Asp(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 197) (Aib², Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 214) (Lys(biotntyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 215)(Ser(n-octanoyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO: 216)(Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO: 217)(Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂; (SEQ ID NO: 218)(Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO: 219)(Aib², Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO: 220)(Aib², Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂; (SEQ ID NO: 221)(Ai^(b2,8), Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO: 222)(Aib^(2,8), Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂; (SEQ ID NO: 223)(Aib^(2,10), Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO: 224)(Aib^(2,10), Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂;  (SEQ ID NO: 225)(Ser(n-octanoyl)¹⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 226)(Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 227)(Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂; (SEQ ID NO: 228)(Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 229)(Aib², Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 230)(Aib², Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂; (SEQ ID NO: 231)(Aib^(2,8), Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 232)(Aib^(2,8), Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂; (SEQ ID NO: 233)(Aib^(2,10), Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 234)(Aib^(2,10), Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂; (SEQ ID NO: 235)(Ser(n-octanoyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO: 236)(Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO: 237)(Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂; (SEQ ID NO: 238)(Glu(NH-hexyl)³, Ser(n-octanoyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO: 239)(Aib², Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO: 240)(Aib², Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂; (SEQ ID NO: 241)(Aib^(2,8), Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO: 242)(Aib^(2,8), Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂; (SEQ ID NO: 243)(Aib^(2,10), Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO: 244)(Aib^(2,10), Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂; (SEQ ID NO: 245)(Ac-Gly¹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 246)(Ac-Gly¹, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO: 247)(Ac-Gly¹, Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂; (SEQ ID NO: 248)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 249) (Ac-Gly¹, Dap(octanesulfonyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 250)(Ac-Gly¹, Dap(octanesulfonyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 251)(Ac-Gly¹, Dap(octanesulfonyl)³, Glu(NH-Hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 252)(Ac-Gly¹, Dap(octanesulfonyl)³, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 253)(Ac-Gly¹, Glu(NH-hexyl)³, Dap(octanesulfonyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 254) (Ac-Gly¹, Cys(S-(CH₂)₉CH₃)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 255) (Ac-Gly¹, Cys(S-(CH₂)₉CH₃)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 256)(Ac-Gly¹, Glu(NH-hexyl)³, Cys(S-(CH₂)₉CH₃)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 257)(Ac-Gly¹, Cys(S-(CH₂)₉CH₃)³, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 258)(Ac-Gly¹, Cys(S-(CH₂)₉CH₃)³, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 259) (Ac-Gly¹, Aib², Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 260)(Ac-Gly¹, Aib², Thz⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 260)(Ac-Gly¹, Aib², 4-Hyp⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 260)(Ac-Gly¹, Aib², Dhp⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 260)(Ac-Gly¹, Aib², Pip⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 260)(Ac-Gly¹, Aib², Tic⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 261)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), Thz⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 261)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), 4-Hyp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 261)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), Dhp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 261)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), Pip⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 261)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), Tic⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 262)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 263)(Ac-Gly¹, Aib², 3-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 263)(Ac-Gly¹, Aib², 4-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 263)(Ac-Gly¹, Aib², Taz⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 263)(Ac-Gly¹, Aib², 2-Thi⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 264)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 264)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 264)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 264)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 265)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 266)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 267) (Ac-Gly¹, Aib⁸, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 268) (Ac-Gly¹, Taz⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 268) (Ac-Gly¹, 3-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 268) (Ac-Gly¹, 4-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 268) (Ac-Gly¹, 2-Thi⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 269)(Ac-Gly¹, Glu(NH-hexyl)^(3,17), Aib⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO: 270)(Ac-Gly¹, Glu(NH-hexyl)^(3,17), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 270)(Ac-Gly¹, Glu(NH-hexyl)^(3,17), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 270)(Ac-Gly¹, Glu(NH-hexyl)^(3,17), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 270)(Ac-Gly¹, Glu(NH-hexyl)^(3,17), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 271)(Ac-Aib¹, Aib^(2,10), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 272)(Ac-Aib¹, Aib^(2,10), Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 259) (Ac-Gly¹, A5c², Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 273)(Ac-Gly¹, A5c², Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 247) (Ac-Gly¹, Glu(1-heptanol)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 274) (Ac-Gly¹, Asp(1-heptanol)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 247) (Ac-Gly¹, Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 274) (Ac-Gly¹, Asp(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO: 275)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)³, Lys(biotinyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO: 276) (Ac-Gly¹, Glu(NH-hexyl)15)hGhrelin(1-28)-NH2;(SEQ ID NO: 277) (Ac-Gly¹, Ser(n-octanoyl)¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 278) (Ac-Gly¹, Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂;(SEQ ID NO: 279)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 280) (Ac-Gly¹, Aib², Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 281)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂;(SEQ ID NO: 282)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 283)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂;(SEQ ID NO: 284)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO: 285)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂;(SEQ ID NO: 286) (Ac-Gly¹, Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 287) (Ac-Gly¹, Ser(n-octanoyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 288) (Ac-Gly¹, Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂;(SEQ ID NO: 289)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 290) (Ac-Gly¹, Aib², Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 291)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂;(SEQ ID NO: 292)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 293)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂;(SEQ ID NO: 294)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO: 295)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂;(SEQ ID NO: 296) (Ac-Gly¹, Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO: 297) (Ac-Gly¹, Ser(n-octanoyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO: 298) (Ac-Gly¹, Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂;(SEQ ID NO: 299)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO: 300) (Ac-Gly¹, Aib², Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO: 301)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂;(SEQ ID NO: 302)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO: 303)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂;(SEQ ID NO: 304)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO: 305)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂;(SEQ ID NO: 306) (Ac-Gly¹, Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 307) (Ac-Gly¹, Ser(n-octanoyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 308) (Ac-Gly¹, Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂;(SEQ ID NO: 309)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 310) (Ac-Gly¹, Aib², Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 311)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂;(SEQ ID NO: 312)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 313)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂;(SEQ ID NO: 314)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO: 315)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂;(SEQ ID NO: 316) (Ac-Gly¹, Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO: 317) (Ac-Gly¹, Ser(n-octanoyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO: 318) (Ac-Gly¹, Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂;(SEQ ID NO: 319)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO: 320) (Ac-Gly¹, Aib², Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO: 321)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂;(SEQ ID NO: 322)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO: 323)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂;(SEQ ID NO: 324)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO: 325)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂;or pharmaceutically acceptable salts thereof.

In yet another aspect, the invention provides a method of treatinggastrointestinal conditions such as gastroesophageal reflux disease,IBS, constipation, ileus, emesis, gastroparesis, and colonicpseudo-obstruction and the like, by administering a therapeuticallyeffective amount of the following peptidyl ghrelin analogs which do notcorrespond to any one of formula (I), (II) or (III):

(SEQ ID NO: 326) (Asp³(NH-heptyl))hGhrelin(1-28)-NH₂ Example #86(SEQ ID NO: 327) (des-Ser²)hGhrelin(1-28)-NH₂; Example #104 or(SEQ ID NO: 328) (des-Gly¹, des-Ser²)hGhrelin(1-28)-NH₂; Example #117(SEQ ID NO: 329) (Aib¹)hGhrelin(1-28)-NH₂; Example #6 (SEQ ID NO: 326)(Asp³(O-hexyl))hGhrelin(1-28)-NH₂; Example #40 (SEQ ID NO: 329)(Aib¹, Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 3)(A5c⁵, Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 330)(Aib^(2,4), Ser³, 4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 95)(n-octanoyl-Gly¹, Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 95)(isobutyryl-Gly¹, Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 95)(n-butyryl-Gly¹, Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 331)(Aib¹, Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 330)(Aib^(2,4), Thr³, 4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 332)(n-octanoyl-Gly¹, Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 332)(isobutyryl-Gly¹, Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 332)(n-butyryl-Gly¹, Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO: 95)(Ac-Gly¹)hGhrelin(1-28)-NH₂; (SEQ ID NO: 95)(Ac-Gly¹, Ser³)hGhrelin(1-28)-NH₂, (SEQ ID NO: 333)Aib², Lys(Myristyl)¹⁷)hGhrelin-(1-28)-NH₂; or (SEQ ID NO: 334)Gly(myristyl)¹-(Aib², Lys(Myristyl)¹⁷]hGhrelin-(1-28)- NH₂;or pharmaceutically acceptable salts thereof.

The peptidyl analog of ghrelin or prodrug thereof may be administeredparenterally, e.g., administered intravenously, subcutaneously, or byimplantation of a sustained release formulation. The peptide analog ofghrelin may also be administered intracerebroventricular (icy)injection. In another embodiment, the peptidyl analog of ghrelin isadministered via oral administration. Particularly preferred peptidylanalogs of ghrelin are those compounds of formula (I) or formula (II) orformula (III), as well as the non-conforming compounds indicated above,as well as each of the compounds that are specifically enumerated hereinand below in the Examples section of the present disclosure, or apharmaceutically acceptable salt thereof.

Accordingly, in one aspect, the invention features a method of treatingileus in a patient, which includes identifying a patient suffering fromor at risk for ileus and administering to the patient a pharmaceuticalcomposition comprising an effective amount of a peptidyl analog ofghrelin. Particularly preferred peptidyl analogs of ghrelin are thosecompounds of formula (I) or formula (II) or formula (III), as well asthe non-conforming compounds indicated above and each of the compoundsthat are specifically enumerated herein and below in the Examplessection of the present disclosure, or a pharmaceutically acceptable saltthereof.

In another aspect, the invention features a method of treatingpost-surgical ileus in a patient. The method includes identifying apatient suffering from post-surgical ileus and administering to thepatient a pharmaceutical composition comprising an effective amount of apeptidyl analog of ghrelin effective to treat ileus in the patient. Theileus can be ileus of any part of the gastrointestinal tract, e.g., thestomach, small intestine, and/or large intestine (e.g., the colon). Thepharmaceutical composition can be administered to the patient via anyroute described herein, e.g., via inhalation (of gaseous compositions);orally; and/or by direct administration to the abdominal cavity of thepatient. Particularly preferred peptidyl analogs of ghrelin are thosecompounds of formula (I) or formula (II) or formula (III), as well asthe non-conforming compounds indicated above and each of the compoundsthat are specifically enumerated herein and below in the Examplessection of the present disclosure, or a pharmaceutically acceptable saltthereof.

The invention also features a method of treating ileus in a patientsuffering from or at risk for ileus not caused by abdominal surgery,e.g., ileus caused by any factor described herein other than abdominalsurgery. The method includes identifying a patient suffering from or atrisk for ileus not caused by abdominal surgery and administering to thepatient a pharmaceutical composition comprising an effective amount of apeptidyl analog of ghrelin effective to treat ileus in the patient.Particularly preferred peptidyl analogs of ghrelin are those compoundsof formula (I) or formula (II) or formula (III), as well as thenon-conforming compounds indicated above and each of the compounds thatare specifically enumerated herein and below in the Examples section ofthe present disclosure, or a pharmaceutically acceptable salt thereof.

In yet another aspect, the invention provides a method of performingsurgery on a patient. The method includes identifying a patient in needof surgery, and before, during, and/or after the surgery, administeringto the patient an effective amount of a peptidyl analog of ghrelinsufficient to treat ileus in the patient. The surgery can be any surgerythat causes and/or puts the patient at risk for ileus. For example, thesurgery can involve manipulation (e.g., touching (directly orindirectly)) of the gastrointestinal tract, e.g., the stomach and/orintestines, e.g., small or large intestine (e.g., the colon), and can bea surgery involving laparotomy or not involving laparotomy (e.g.,surgeries involving laparoscopy). In certain embodiments, the surgerycan be transplant surgery or non-transplant surgery, e.g., surgeryinvolving any organ(s) or tissue(s) in the abdomen, e.g., surgery of theurogenital system (e.g., kidneys, ureter, and/or bladder; andreproductive organs (e.g., uterus, ovaries, and/or fallopian tubes));the digestive system (e.g., the stomach, small intestine, largeintestine (e.g., the colon), appendix, gallbladder, liver, spleen,and/or pancreas); the lymphatic system; the respiratory system (e.g.,the lungs); the diaphragm; surgery to treat cancer of any organ ortissue within the abdomen; endometrial surgery; and orthopedicsurgeries, e.g., hip surgery. Particularly preferred peptidyl analogs ofghrelin are those compounds of formula (I) or formula (II) or formulaIII as well as each of the compounds that are specifically enumeratedherein and below in the Examples section of the present disclosure, or apharmaceutically acceptable salt thereof.

In still another aspect, the invention provides a method of treatingileus in a patient, which includes identifying a patient suffering fromor at risk for ileus and administering to the patient an effectiveamount of a peptidyl analog of ghrelin for treatment or prevention ofileus. Particularly preferred peptidyl analogs of ghrelin are thosecompounds of formula (I) or formula (II) or formula (III), as well asthe non conforming compounds indicated above and each of the compoundsthat are specifically enumerated herein and below in the Examplessection of the present disclosure, or a pharmaceutically acceptable saltthereof.

In another aspect, the invention features a method of treating emesis ina patient, which includes identifying a patient suffering from or atrisk for emesis and administering to the patient a pharmaceuticalcomposition comprising an effective amount of a peptidyl analog ofghrelin. Particularly preferred peptidyl analogs of ghrelin are thosecompounds of formula (I) or formula (II) or formula (III), as well asthe non-conforming compounds indicated above and each of the compoundsthat are specifically enumerated herein and below in the Examplessection of the present disclosure, or a pharmaceutically acceptable saltthereof.

In yet another aspect, the invention features a method of treatingemesis provoked by or associated with the administration of anti-cancerchemotherapeutic agents in a patient, which includes identifying apatient suffering from or at risk for emesis provoked by or associatedwith the administration of anti-cancer chemotherapeutic agents andadministering to the patient a pharmaceutical composition comprising atherapeutically effective amount of a peptidyl analog of ghrelin.Particularly preferred peptidyl analogs of ghrelin are those compoundsof formula (I) or formula (II) or formula (III), as well as thenon-conforming compounds indicated above and each of the compounds thatare specifically enumerated herein and below in the Examples section ofthe present disclosure, or a pharmaceutically acceptable salt thereof.

In another aspect, the invention features a method of treatinggastroparesis in a patient, which includes identifying a patientsuffering from or at risk for gastroparesis and administering to thepatient a pharmaceutical composition comprising an effective amount of apeptidyl analog of ghrelin. Particularly preferred peptidyl analogs ofghrelin are those compounds of formula (I) or formula (II) or formula(III), as well as the non-conforming compounds indicated above and eachof the compounds that are specifically enumerated herein and below inthe Examples section of the present disclosure, or a pharmaceuticallyacceptable salt thereof.

In yet another aspect, the invention features a method of treatinggastroparesis resulting from diabetes in a patient, which includesidentifying a patient suffering from or at risk for diabeticgastroparesis and administering to the patient a pharmaceuticalcomposition comprising an effective amount of a peptidyl analog ofghrelin. The diabetes may be Type I or Type II diabetes. Particularlypreferred peptidyl analogs of ghrelin are those compounds of formula (I)or formula (II) or formula (III), as well as the non-conformingcompounds indicated above and each of the compounds that arespecifically enumerated herein and below in the Examples section of thepresent disclosure, or a pharmaceutically acceptable salt thereof.

In a further aspect, the present invention provides the use of atherapeutically effective amount of a peptidyl ghrelin analog compoundaccording formula (I) or formula (II) or formula (III) as definedhereinabove, as well as the non-conforming compounds indicated above andeach of the compounds specifically enumerated herein and below, orpharmaceutically acceptable salts thereof, for the manufacture of amedicament useful to treat gastrointestinal conditions such asgastroesophageal reflux disease, IBS, constipation, ileus, emesis,gastroparesis, and colonic pseudo-obstruction and the like. In yetanother embodiment, the gastrointestinal conditions treated are ileus,emesis and gastroparesis. In yet another embodiment, the ilieus ispost-operative ileus, the emesis is associated with the administrationof anti-cancer chemotherapeutic agents and the gastroparesis isassociated with diabetes.

In yet another aspect, the present invention provides a method ofeliciting an agonist or an antagonist effect from a ghrelin receptor ina subject in need thereof which comprises administering to said subjectan effective amount of a compound of formula (I) or formula (II) orformula (III) as defined hereinabove, as well as the non-conformingcompounds indicated above and each of the compounds specificallyenumerated herein and below or pharmaceutically acceptable saltsthereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: shows the schematic presentation of the methods used to studygastric emptying in a rat model;

FIG. 2: shows the effect on gastric emptying in normal rats for nativeghrelin and Example 19;

FIG. 3: shows the percent decrease in gastric emptying due topost-operative ileus alone and in combination with morphine; and

FIG. 4: shows the effect on gastric emptying in post-operative ileus ratmodel for native ghrelin and Example 19;

FIG. 5: shows the effect on gastric emptying in post-operative ileus andmorphine rat model for native ghrelin and Example 19.

DETAILED DESCRIPTION

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Suitable methods and materialsare described below, although methods and materials similar orequivalent to those described herein can be used in the practice ortesting of the present invention. All publications, patent applications,patents, and other references mentioned herein are incorporated byreference in their entirety. In case of conflict, the presentspecification, including definitions, will control. The materials,methods, and examples are illustrative only and not intended to belimiting.

Other features and advantages of the invention will be apparent from thefollowing description of the preferred embodiments and from the claims.Certain amino acids present in compounds of the invention can be and arerepresented herein as follows:

Nomenclature and Abbreviations

Symbol Meaning Abu α-aminobutyric acid Acc 1-amino-1-cyclo(C₃-C₉)alkylcarboxylic acid A3c 1-amino-1-cyclopropanecarboxylic acid A4c1-amino-1-cyclobutanecarboxylic acid A5c1-amino-1-cyclopentanecarboxylic acid A6c1-amino-1-cyclohexanecarboxylic acid Act4-amino-4-carboxytetrahydropyran having the structure:

Aib α-aminoisobutyric acid Aic 2-aminoindan-2-carboxylic acid Ala or Aalanine β-Ala beta-alanine Apc denotes the structure:

Arg or R arginine hArg homoarginine Asn or N asparagine Asp or Daspartic acid Ava 5-amino-n-valeric acid D-Bal D-3-benzothienylalaninehaving the structure:

D-Bip D-4,4′-biphenylalanine having the structure:

D-Bpa D-4-benzoylphenylalanine having the structure:

Cha β-cyclohexylalanine Cys or C cysteine hCys L-homocysteine Dab2,4-diaminobutyric acid Dap 2,3-diaminopropionic acid Dap(octanoyl)denotes the structure:

Dhp 3,4-dihydroproline Dip β,β-diphenylalanine having the structure:

Dmt 5,5-dimethylthiazolidine-4-carboxylic acid 2-Fua β-(2-furyl)-alanineGln or Q glutamine Glu or E glutamic acid Gly or G glycine His or Hhistidine 3-Hyp trans-3-hydroxy-L-proline, i.e., (2S,3S)-3-hydroxypyrrolidine-2-carboxylic acid 4-Hyp 4-hydroxyproline, i.e.,(2S, 4R)- 4-hydroxypyrrolidine-2-carboxylic acid Ile or I isoleucine Incindoline-2-carboxylic acid Inp isonipecotic acid Ktp 4-ketoproline Leuor L leucine hLeu homoleucine Lys or K lysine Lys (biotinyl) lysinebiotinyl having the structure:

Met or M methionine 1-Nal β-(1-naphthyl)-L-alanine 2-Nalβ-(2-naphthyl)-L-alanine Nle norleucine Nva norvaline Oicoctahydroindole-2-carboxylic acid Orn ornithine 2-Palβ-(2-pyridiyl)alanine 3-Pal β-(3-pyridiyl)alanine 4-Palβ-(4-pyridiyl)alanine Phe or F phenylalanine hPhe homophenylalanine Pffpentafluorophenylalanine having the structure:

Pip pipecolic acid Pim 2′-(4-phenyl)imidazolyl having the structure:

Pro or P proline Ser or S serine Taz β-(4-thiazolyl)alanine having thestructure:

2-Thi β-(2-thienyl)alanine 3-Thi β-(3-thienyl)alanine Thr or T threonineThz thiazolidine-4-carboxylic acid Tic1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Tle tert-leucine Trp orW tryptophan Tyr or Y tyrosine Val or V valine

When a non-amino acid imidazole moiety (e.g., Pim, defined above) ispresent at the C-terminus of a compound of the invention, it isunderstood that the imidazole moiety is attached to the adjacent aminoacid via a pseudo-peptide bond (w), wherein a bond is form between theposition 2 carbon of the imidazole ring and the alpha carbon of theamino acid. For example, in the case where the adjacent amino acid isD-tryptophan (D-Trp) and the imidazole moiety is Pim, the C-terminus ofthe peptide would appear as follows:

As used herein, Acc encompasses an amino acid selected from the group of1 amino-1-cyclopropanecarboxylic acid (A3c);1-amino-1-cyclobutanecarboxylic acid (A4c);1-amino-1-cyclopentanecarboxylic acid (A5c);1-amino-1-cyclohexanecarboxylic acid (A6c);1-amino-1-cycloheptanecarboxylic acid (A7c);1-amino-1-cyclooctanecarboxylic acid (A8c); and1-amino-1-cyclononanecarboxylic acid (A9c). As used herein, a “peptidylanalog of ghrelin” encompasses ghrelin analogues and peptidyl analogsthereof which can be used to practice the therapeutic method of thepresent invention including, but not limited to, the followingcompounds:

(SEQ ID NO: 1) (Dap³(Octanesulfonyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  2)(Aib², A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  3)(A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  4) (Aib^(2,6))hGhrelin(1-28)-NH₂;(SEQ ID NO:  5) (Aib², A5c¹²)hGhrelin(1-28)-NH₂; (SEQ ID NO:  6)(Aib², A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  7)(Aib², A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  4)(Aib², Act⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  8)(Aib², 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Dmt⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Thz⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  10)(A5c²)hGhrelin(1-28)-NH₂; (SEQ ID NO:  10) (Act²)hGhrelin(1-28)-NH₂;(SEQ ID NO:  2) (Aib², A5c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  2)(Aib², A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  2)(Aib^(2,5))hGhrelin(1-28)-NH₂; (SEQ ID NO:  2)(Aib², hLeu⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  2)(Aib², Cha⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  4)(Aib^(2,6))hGhrelin(1-28)-NH₂; (SEQ ID NO:  4)(Aib², Act⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  4)(Aib², Thr⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  4)(Aib², Abu⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², 4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Thz⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Pip⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Dhp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Ktp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  11)(Aib^(2,8))hGhrelin(1-28)-NH₂; (SEQ ID NO:  8)(Aib², 2-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  8)(Aib², 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  8)(Aib², 4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  8)(Aib², Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  8)(Aib², 2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  8)(Aib², 2-Fua⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  8)(Aib², Apc⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  8)(Aib^(2,9))hGhrelin(1-28)-NH₂; (SEQ ID NO:  12)(Aib^(2,10))hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Tic⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  13)(Aib⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  3) (A5c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  3) (A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  13)(Act⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  14) (3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  15) (Dmt⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  15)(Thz⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  3) (Aib⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  3) (hLeu⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  3)(Cha⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  13) (Thr⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  13) (Abu⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  15)(4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  15) (Pip⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  15) (Dhp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  15)(Ktp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  16) (Aib⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO:  14) (2-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  14)(4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  14) (Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  14) (2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  14)(2-Fua⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  14) (Apc⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  14) (Aib⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  17)(Aib¹⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO:  18)(Aib², Dap³(Octanesulfonyl), A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  19)(Dap³(Octanesulfonyl), A6c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  20)(Aib^(2,6), Dap³(Octanesulfonyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  21)(Aib², Dap³(Octanesulfonyl), A5c¹²)hGhrelin(1-28)-NH₂; (SEQ ID NO:  22)(Aib², Dap³(Octanesulfonyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  23)(Aib², Dap³(Octanesulfonyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  20) (Aib², Dap³(Octanesulfonyl), Act⁶⁾hGhrelin(1-28)-NH₂;(SEQ ID NO:  24) (Aib², Dap³(Octanesulfonyl), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  25) (Aib², Dap³(Octanesulfonyl), Dmt⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  25) (Aib², Dap³(Octanesulfonyl), Thz⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  26) (A5c², Dap³(Octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO:  26) (Act², Dap³(Octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO:  18) (Aib², Dap³(Octanesulfonyl), A5c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  18) (Aib^(2,5), Dap³(Octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO:  18) (Aib², Dap³(Octanesulfonyl), hLeu⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  18) (Aib², Dap³(Octanesulfonyl), Cha⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  20) (Aib^(2,6), Dap³(Octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO:  20) (Aib², Dap³(Octanesulfonyl), Thr⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  20) (Aib², Dap³(Octanesulfonyl), Abu⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  25) (Aib², Dap³(Octanesulfonyl), 4-Hyp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  25) (Aib², Dap³(Octanesulfonyl), Pip⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  25) (Aib², Dap³(Octanesulfonyl), Dhp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  25) (Aib², Dap³(Octanesulfonyl), Ktp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  27) (Aib^(2,8), Dap³(Octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO:  24) (Aib2, Dap³(Octanesulfonyl), 2-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  24) (Aib², Dap³(Octanesulfonyl), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  24) (Aib², Dap³(Octanesulfonyl), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  24) (Aib², Dap³(Octanesulfonyl), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  24) (Aib², Dap³(Octanesulfonyl), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  24) (Aib², Dap³(Octanesulfonyl), 2-Fua⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  24) (Aib², Dap³(Octanesulfonyl), Apc⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  24) (Aib^(2,9), Dap³(Octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO:  28) (Aib^(2,10), Dap³(Octanesulfonyl))hGhrelin(1-28)-NH₂;(SEQ ID NO:  19) (Dap³(Octanesulfonyl), A6c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  29) (Dap³(Octanesulfonyl), Aib⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  30) (Dap³(Octanesulfonyl), A5c¹²)hGhrelin(1-28)-NH₂;(SEQ ID NO:  31) (Dap³(Octanesulfonyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  32) (Dap³(Octanesulfonyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  29) (Dap³(Octanesulfonyl), Act⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  33) (Dap³(Octanesulfonyl), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  34) (Dap³(Octanesulfonyl), Dmt⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  34) (Dap³(Octanesulfonyl), Thz⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  19) (Dap³(Octanesulfonyl), A5c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  19) (Dap³(Octanesulfonyl), Aib⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  19) (Dap³(Octanesulfonyl), hLeu⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  19) (Dap³(Octanesulfonyl), Cha⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  29) (Dap³(Octanesulfonyl), Thr⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  29) (Dap³(Octanesulfonyl), Abu⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  34) (Dap³(Octanesulfonyl), 4-Hyp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  34) (Dap³(Octanesulfonyl), Pip⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  34) (Dap³(Octanesulfonyl), Dhp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  34) (Dap³(Octanesulfonyl), Ktp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  35) (Dap³(Octanesulfonyl), Aib⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO:  33) (Dap³(Octanesulfonyl), 2-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  33) (Dap³(Octanesulfonyl), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  33) (Dap³(Octanesulfonyl), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  33) (Dap³(Octanesulfonyl), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  33) (Dap³(Octanesulfonyl), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  33) (Dap³(Octanesulfonyl), 2-Fua⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  33) (Dap³(Octanesulfonyl), Apc⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  33) (Dap³(Octanesulfonyl), Aib⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  36) (Dap³(Octanesulfonyl), Aib¹⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO:  31) (Dap³(Octanesulfonyl), A5c12, Orn15)hGhrelin(1-28)-NH₂;(SEQ ID NO:  31) (Dab³(Octanesulfonyl), A5c12, Orn15)hGhrelin(1-28)-NH₂;(SEQ ID NO:  37) (Aib², A6c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  38) (A6c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  39) (Aib^(2,6), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  39) (Aib², Act⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  40) (Aib², 3-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  41) (Aib², Dmt⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  41) (Aib², Thz⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  37) (Aib², A5c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  37) (Aib^(2,5), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  37) (Aib², hLeu⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  37) (Aib², Cha⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  39) (Aib^(2,6), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  39) (Aib², Thr⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  39) (Aib², Abu⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  41) (Aib², 4-Hyp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  41) (Aib², Pip⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  41) (Aib², Dhp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  41) (Aib², Ktp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  42) (Aib^(2,8), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  40) (Aib², 2-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  40) (Aib², 3-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  40) (Aib², 4-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  40) (Aib², Taz⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  40) (Aib², 2-Thi⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  40) (Aib², 2-Fua⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  40) (Aib², Apc⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  43) (Aib^(2,10), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  32) (Dap³(Octanesulfonyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  32) (Dab³(Octanesulfonyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  44) (Aib², A6c⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  45) (A6c⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  46) (Aib^(2,6), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  46) (Aib², Act⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  47) (Aib², 3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  48) (Aib², Dmt⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  48) (Aib², Thz⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  44) (Aib², A5c^(5,12), Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  44) (Aib^(2,5), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  44) (Aib², hLeu⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  44) (Aib², Cha⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  46) (Aib^(2,6), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  46) (Aib², Thr⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  46) (Aib², Abu⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  48) (Aib², 4-Hyp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  48) (Aib², Pip⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  48) (Aib², Dhp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  48) (Aib², Ktp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  49) (Aib^(2,8), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  47) (Aib², 2-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  47) (Aib², 3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  47) (Aib², 4-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  47) (Aib², Taz⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  47) (Aib², 2-Thi⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  47) (Aib², 2-Fua⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  47) (Aib², Apc⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  47) (Aib^(2,9), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  50) (Aib^(2,10), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  38) (A6c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  51) (Aib⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  51) (Act⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  52) (3-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  53) (Dmt⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  53) (Thz⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  38) (A5c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  38) (Aib⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  38) (hLeu⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  38) (Cha⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  51) (Aib⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  51) (Thr⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  51) (Abu⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  53) (4-Hyp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  53) (Pip⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  53) (Dhp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  53) (Ktp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  54) (Aib⁸, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  52) (2-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  52) (3-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  52) (4-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  52) (Taz⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  52) (2-Thi⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  52) (2-Fua⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  52) (Apc⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  52) (Aib⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  55) (Aib¹⁰, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  56) (Aib⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  45) (A5c⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  56) (Act⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  57) (3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  58) (Dmt⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  58) (Thz⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  45) (Aib⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  45) (hLeu⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  45) (Cha⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  56) (Thr⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  56) (Abu⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  58) (4-Hyp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  58) (Pip⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  58) (Dhp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  58) (Ktp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  59) (Aib⁸, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  57) (2-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  57) (3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  57) (4-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  57) (Taz⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  57) (2-Thi⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  57) (2-Fua⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  57) (Apc⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  57) (Aib⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  60) (Aib¹⁰, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  61) (Aib², Glu³(NH-Hexyl), A6c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  62) (Glu³(NH-Hexyl), A6c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  63) (Aib^(2,6), Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂;(SEQ ID NO:  63) (Aib², Glu³(NH-Hexyl), Act⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  64) (Aib², Glu³(NH-Hexyl), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  65) (Aib², Glu³(NH-Hexyl), Dmt⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  65) (Aib², Glu³(NH-Hexyl), Thz⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  61) (Aib², Glu³(NH-Hexyl), A5c⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  61) (Aib^(2,5), Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  61) (Aib², Glu³(NH-Hexyl), hLeu⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  2) (Aib², Cha⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  63)(Aib^(2,6), Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  63)(Aib², Glu³(NH-Hexyl), Thr⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  63)(Aib², Glu³(NH-Hexyl), Abu⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  65)(Aib², Glu³(NH-hexyl), 4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  65)(Aib², Glu³(NH-Hexyl), Pip⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  65)(Aib², Glu³(NH-Hexyl), Dhp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  65)(Aib², Glu3(NH-Hexyl), Ktp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  27)(Aib^(2,8), Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  64)(Aib², Glu³(NH-Hexyl), 2-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  64)(Aib², Glu³(NH-Hexyl), 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  64)(Aib², Glu³(NH-Hexyl), 4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  64)(Aib², Glu³(NH-Hexyl), Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  64)(Aib², Glu³(NH-Hexyl), 2-Thi9)hGhrelin(1-28)-NH₂; (SEQ ID NO:  64)(Aib², Glu³(NH-Hexyl), 2-Fua9)hGhrelin(1-28)-NH₂; (SEQ ID NO:  64)(Aib², Glu³(NH-Hexyl), Apc9)hGhrelin(1-28)-NH₂; (SEQ ID NO:  64)(Aib^(2,9), Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  28)(Aib^(2,10), Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  66)(Glu³(NH-Hexyl), Aib⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  62)(Glu³(NH-Hexyl), A5c⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  66)(Glu³(NH-Hexyl), Act⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  67)(Glu³(NH-Hexyl), 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  68)(Glu³(NH-Hexyl), Dmt⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  68)(Glu³(NH-Hexyl), Thz⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  62)(Glu³(NH-Hexyl), Aib⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  62)(Glu³(NH-Hexyl), hLeu⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  62)(Glu³(NH-Hexyl), Cha⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  66)(Glu³(NH-Hexyl), Thr⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  66)(Glu³(NH-Hexyl), Abu⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  68)(Glu³(NH-Hexyl), 4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  68)(Glu³(NH-Hexyl), Pip⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  68)(Glu₃(NH-Hexyl), Dhp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  68)(Glu³(NH-Hexyl), Ktp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  35)(Glu³(NH-hexyl), Aib⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO:  67)(Glu³(NH-Hexyl), 2-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  67)(Glu³(NH-Hexyl), 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  67)(Glu³(NH-Hexyl), 4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  67)(Glu³(NH-Hexyl), Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  67)(Glu³(NH-Hexyl), 2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  67)(Glu³(NH-Hexyl), 2-Fua⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  67)(Glu³(NH-Hexyl), Apc⁹)hGhrelin(1-28)-NH₂;  (SEQ ID NO:  67)(Glu³(NH-Hexyl), Aib⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  36)(Glu³(NH-Hexyl), Aib¹⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO:  69)(Aib², Glu³(NH-Hexyl), A6c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  70) (A6c⁵, Glu³(NH-Hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  71)(Aib^(2,6), Glu³(NH-Hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  71)(Aib², Glu³(NH-Hexyl), Act⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  72)(Aib², Glu³(NH-Hexyl), 3-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  73)(Aib², Glu³(NH-Hexyl), Dmt⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  73)(Aib², Glu³(NH-Hexyl), Thz⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  69)(Aib2, Glu3(NH-Hexyl), A5c⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  69)(Aib^(2,5), Glu³(NH-Hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  37) (Aib², hLeu⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  69)(Aib², Glu³(NH-Hexyl), Cha⁵, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  71)(Aib^(2,6), Glu³(NH-Hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  71)(Aib², Glu³(NH-Hexyl), Thr⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  71)(Aib², Glu³(NH-Hexyl), Abu⁶, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  73)(Aib², Glu³(NH-Hexyl), 4-Hyp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  73)(Aib², Glu³(NH-Hexyl), Pip⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  73)(Aib², Glu³(NH-Hexyl), Dhp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  73)(Aib², Glu³(NH-Hexyl), Ktp⁷, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  74)(Aib^(2,8), Glu³(NH-Hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  72)(Aib², Glu³(NH-Hexyl), 2-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  72)(Aib², Glu³(NH-Hexyl), 3-Pal⁹, A5^(c12), Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  72)(Aib², Glu³(NH-Hexyl), 4-Pal⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  72)(Aib², Glu³(NH-Hexyl), Taz⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  72)(Aib², Glu³(NH-Hexyl), 2-Thi⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  72)(Aib², Glu³(NH-Hexyl), 2-Fua⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  72)(Aib², Glu³(NH-Hexyl), Apc⁹, A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  72)(Aib^(2,9), Glu³(NH-Hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  75)(Aib^(2,12), Glu³(NH-Hexyl),4-Pal⁹, Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  76)(Aib^(2,10), Glu³(NH-Hexyl), A5c¹², Orn¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  77)(Aib², Glu³(NH-Hexyl), A6c⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  78) (Glu³(NH-Hexyl), A6c⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  79)(Aib^(2,6), Glu³(NH-Hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  79)(Aib², Glu³(NH-Hexyl), Act⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  80)(Aib², Glu³(NH-Hexyl), 3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  81)(Aib², Glu³(NH-Hexyl), Dmt⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  81)(Aib², Glu³(NH-Hexyl), Thz⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  77)(Aib², Glu³(NH-Hexyl), A5c^(5,12), Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  77)(Aib^(2,5), Glu³(NH-Hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  77)(Aib², Glu³(NH-Hexyl), hLeu⁵, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  77)(Aib², Glu³(NH-Hexyl), Cha⁵, A5c¹², Ap^(c16))hGhrelin(1-28)-NH₂;(SEQ ID NO:  79)(Aib^(2,6), Glu³(NH-Hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  79)(Aib², Glu³(NH-Hexyl), Thr⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  79)(Aib², Glu³(NH-Hexyl), Abu⁶, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  81)(Aib², Glu³(NH-Hexyl), 4-Hyp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  81)(Aib², Glu³(NH-Hexyl), Pip⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  81)(Aib², Glu³(NH-Hexyl), Dhp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  81)(Aib², Glu³(NH-Hexyl), Ktp⁷, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  82)(Aib^(2,8), Glu³(NH-Hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  80)(Aib², Glu³(NH-Hexyl), 2-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  80)(Aib², Glu³(NH-Hexyl), 3-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  80)(Aib², Glu³(NH-Hexyl), 4-Pal⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  80)(Aib², Glu³(NH-Hexyl), Taz⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  80)(Aib², Glu³(NH-Hexyl), 2-Thi⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  80)(Aib², Glu³(NH-Hexyl), 2-Fua⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  80)(Aib², Glu³(NH-Hexyl), Apc⁹, A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  80)(Aib^(2,9), Glu³(NH-Hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  83)(Aib^(2,10), Glu³(NH-Hexyl), A5c¹², Apc¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  1) (Glu³(O-hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  10)(Aib²)hGhrelin(1-28)-NH₂; (SEQ ID NO:  1)(Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  84)(Aib², Glu³(O-Hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  85)(Aib¹, Glu³(O-Hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  84)(Aib², Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  1)(Dap³(1-Octanesulfonyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  84)(Aib², Dap³(1-Octanesulfonyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  85)(Aib¹, Dap³(1-Octanesulfonyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  86)(Ava², Dap³(1-Octanesulfonyl))hGhrelin(2-28)-NH₂; (SEQ ID NO:  87)(Ac-Gly¹)hGhrelin(1-5)-NH₂; (SEQ ID NO:  88) (Ac-Gly¹)hGhrelin(1-6)-NH₂;(SEQ ID NO:  89) (Ac-Gly¹)hGhrelin(1-7)-NH₂; (SEQ ID NO:  90)(Ac-Gly¹, Aib²)hGhrelin(1-28)-NH₂; (SEQ ID NO:  91)(Ac-Gly¹, Aib², Glu³(NH-Hexyl))hGhrelin(1-5)-NH₂; (SEQ ID NO:  92)(Ac-Gly¹, Aib², Glu³(NH-Hexyl))hGhrelin(1-6)-NH₂; (SEQ ID NO:  93)(Ac-Gly¹, Aib², Glu³(NH-Hexyl))hGhrelin(1-7)-NH₂; (SEQ ID NO:  335)(Ac-Gly¹, Aib², Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂; (SEQ ID NO:  94)(Ac-Gly¹, Aib², Glu³(NH-Hexyl), Arg⁸)hGhrelin(1-8)-NH₂; (SEQ ID NO:  94)(Ac-Gly¹, Aib², Glu³(NH-Hexyl), Lys⁸)hGhrelin(1-8)-NH₂; (SEQ ID NO:  95)(n-Butyryl-Gly¹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  335)(n-Butyryl-Gly¹, Aib², Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂;(SEQ ID NO:  95) (Isobutyry1-Gly¹)hGhrelin(1-28)-NH₂; or(SEQ ID NO:  95) (n-Octanoyl-Gly¹)hGhrelin(1-28)-NH₂, ora pharmaceutically acceptable salt thereof. (SEQ ID NO:  1)Cys³(S(CH₂)₉CH₃)hGhrelin(1-28)-NH₂; (SEQ ID NO:  10)(Aib², Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  4)(Aib^(2,6), Ser³)hGhrelin(1-28)-NH₂ (SEQ ID NO:  8)(Aib², Ser³, 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Ser³, Thz⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  2)(Aib², Ser³, Cha⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  4)(Aib², Ser³, Abu⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Ser³, 4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  8)(Aib², Ser³, Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Ser³, Dhp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  11)(Aib^(2,8), Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Ser³, Pip⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  96)(Ac-Gly¹, Aib^(2,10), Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  12)(Aib^(2,10), Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  97)(n-Butyryl-Gly¹, Aib², Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  97)(Ac-Gly¹, Aib², Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Ser³, Tic⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  98)(Ac-Gly¹, Aib², Ser³, Arg⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO:  16)(Ser³, Aib⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO:  14)(Ser³, Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  14)(Ser³, 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  14)(Ser³, 4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  8)(Aib², Ser³, 2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  14)(Ser³, 2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  15)(Ser³, 4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  9)(Aib², Ser³, Tic⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  99)(Aib², Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  99)(Aib^(2,6), Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  100)(A5c⁵, Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  101)(Aib², Thr³, 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  102)(Aib², Thr³, Thz⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  103)(Aib², Thr³, Cha⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  99)(Aib², Thr³, Abu⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  102)(Aib², Thr³, 4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  101)(Aib², Thr³, Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  102)(Aib², Thr³, Dhp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  11)(Aib^(2,8), Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  102)(Aib², Thr³, Pip⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  104)(Ac-Gly¹, Aib^(2,10), The)hGhrelin(1-28)-NH₂; (SEQ ID NO:  106)(Aib^(2,10), Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  105)(n-Butyryl-Gly¹, Aib², Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  105)(Ac-Gly¹, Aib², Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  102)(Aib², Thr³, Tic⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  90)(Ac-Gly¹, Aib², Thr³, Arg⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO:  107)(Thr³, Aib⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO:  108)(Thr³, Taz⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  108)(Thr³, 3-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  108)(Thr³, 4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  101)(Aib², Thr³, 2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  108)(Thr³, 2-Thi⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  109)(Thr³, 4-Hyp⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  102)(Aib², Thr³, Tic⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  110)(Ac-Gly¹, Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂; or (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-3-Pal-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-4-Pal-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-Orn-Lys-NH₂; (SEQ ID NO:  111)H-Inp-D-Bip-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-Thr(Bzl)-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  111)H-Inp-D-Dip-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  111)H-Inp-D-Bpa-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  114)H-Inp-D-2-Nal-D-Bpa-Phe-Lys-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-3-Pal-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-4-Pal-NH₂; (SEQ ID NO:  116)H-Inp-D-1-Nal-D-Trp-3-Pal-NH₂; (SEQ ID NO:  117)H-Inp-D-Bip-D-Trp-Phe-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-Thr(Bzl)-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-Pff-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-2-Thi-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-Taz-NH₂; (SEQ ID NO:  117)H-Inp-D-Dip-D-Trp-Phe-NH₂; (SEQ ID NO:  118)H-Inp-D-2-Nal-D-Dip-Phe-NH₂; (SEQ ID NO:  119)H-Inp-D-Bal-D-Trp-Phe-NH₂; (SEQ ID NO:  118)H-Inp-D-2-Nal-D-Bal-Phe-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-3-Pal-Lys-NH₂; (SEQ ID NO:  120)H-Inp-D-Trp-D-2-Nal(Ψ)-Pim; (SEQ ID NO:  121)H-Inp-D-Bal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  111)H-Inp-D-Bal-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  122)H-Inp-D-2-Nal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO:  122)H-Inp-D-1-Nal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO:  122)H-Inp-D-Bal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO:  123)H-Apc-D-2-Nal-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  124)H-Apc-D-1-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  116)H-Inp-D-1-Nal-D-Trp-2-Thi-NH₂; (SEQ ID NO:  125)H-Apc-D-1-Nal-D-Trp-Phe-NH₂; (SEQ ID NO:  126)H-Inp-D-2-Nal-D-Trp(Ψ)-Pim; (SEQ ID NO:  126)H-Inp-D-1-Nal-D-Trp(Ψ)-Pim; (SEQ ID NO:  126) H-Inp-D-Bal-D-Trp(Ψ)-Pim;(SEQ ID NO:  127) H-Aib-D-Ser(Bzl)-D-Trp(Ψ)-Pim; (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  121)H-Inp-D-Bal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  124)H-Apc-D-1-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  128)H-Apc-D-Bal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  128)H-Apc-D-Bal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  123)H-Apc-D-Bal-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  129)H-Apc-D-1-Nal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO:  130)H-Apc-D-Bal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO:  129)H-Apc-D-1-Nal-D-1-Nal-Phe-Apc-NH₂; (SEQ ID NO:  129)H-Apc-D-1-Nal-D-2-Nal-Phe-Apc-NH₂; (SEQ ID NO:  131)H-Apc-D-1-Nal-D-1-Nal-Phe-Lys-NH₂; (SEQ ID NO:  130)H-Apc-D-Bal-D-1-Nal-Phe-Apc-NH₂; (SEQ ID NO:  130)H-Apc-D-Bal-D-2-Nal-Phe-Apc-NH₂; (SEQ ID NO:  132)H-Apc-D-Bal-D-1-Nal-Phe-Lys-NH₂; (SEQ ID NO:  132)H-Apc-D-Bal-D-2-Nal-Phe-Lys-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-2-Thi-NH₂; (SEQ ID NO:  125)H-Apc-D-Bal-D-Trp-Phe-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-Taz-NH₂; (SEQ ID NO:  144)H-Apc-D-Bal-D-Trp-2-Thi-NH₂; (SEQ ID NO:  144)H-Apc-D-Bal-D-Trp-Taz-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-2-Thi-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-Taz-NH₂; (SEQ ID NO:  135)H-Inp-D-1-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  135)H-Inp-D-Bal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  136)H-Apc-D-1-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  136)H-Apc-D-Bal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  137)H-Apc-D-1-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  124)H-Apc-D-1-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-2-Pal-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-3-Pal-NH₂; (SEQ ID NO:  137)H-Apc-D-1-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  124)H-Apc-D-1-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-3-Thi-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-4-Pal-NH₂; (SEQ ID NO:  137)H-Apc-D-1-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  124)H-Apc-D-1-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-Pff-NH₂; (SEQ ID NO:  138)H-Apc-D-2-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  139)H-Apc-D-2-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-2-Pal-NH₂; (SEQ ID NO:  138)H-Apc-D-2-Nal-D-Trp-2-Thi-Apc-NH₂; (SEQ ID NO:  139)H-Apc-D-2-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-3-Pal-NH₂; (SEQ ID NO:  138)H-Apc-D-2-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  139)H-Apc-D-2-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-3-Thi-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-4-Pal-NH₂; (SEQ ID NO:  138)H-Apc-D-2-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  139)H-Apc-D-2-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-Pff-NH₂; (SEQ ID NO:  136)H-Apc-D-2-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  139)H-Apc-D-2-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  140)H-Apc-D-Bal-D-Bal-2-Fua-Apc-NH₂; (SEQ ID NO:  141)H-Apc-D-Bal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-2-Fua-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-2-Pal-NH₂; (SEQ ID NO:  140)H-Apc-D-Bal-D-Bal-2-Thi-Apc-NH₂; (SEQ ID NO:  141)H-Apc-D-Bal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-2-Thi-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-3-Pal-NH₂; (SEQ ID NO:  140)H-Apc-D-Bal-D-Bal-3-Thi-Apc-NH₂; (SEQ ID NO:  141)H-Apc-D-Bal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-3-Thi-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-4-Pal-NH₂; (SEQ ID NO:  140)H-Apc-D-Bal-D-Bal-Pff-Apc-NH₂; (SEQ ID NO:  141)H-Apc-D-Bal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-Pff-NH₂; (SEQ ID NO:  130)H-Apc-D-Bal-D-Bal-Phe-Apc-NH₂; (SEQ ID NO:  132)H-Apc-D-Bal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-Phe-NH₂; (SEQ ID NO:  140)H-Apc-D-Bal-D-Bal-Taz-Apc-NH₂; (SEQ ID NO:  141)H-Apc-D-Bal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-Taz-NH₂; (SEQ ID NO:  143)H-Apc-D-Bal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  128)H-Apc-D-Bal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  144)H-Apc-D-Bal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  144)H-Apc-D-Bal-D-Trp-2-Pal-NH₂; (SEQ ID NO:  144)H-Apc-D-Bal-D-Trp-3-Pal-NH₂; (SEQ ID NO:  143)H-Apc-D-Bal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  128)H-Apc-D-Bal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  144)H-Apc-D-Bal-D-Trp-3-Thi-NH₂; (SEQ ID NO:  144)H-Apc-D-Bal-D-Trp-4-Pal-NH₂; (SEQ ID NO:  143)H-Apc-D-Bal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  128)H-Apc-D-Bal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  144)H-Apc-D-Bal-D-Trp-Pff-NH₂; (SEQ ID NO:  145)H-Inp-D-1-Nal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO:  146)H-Inp-D-1-Nal-D-Bal-2-Fua-NH₂; (SEQ ID NO:  145)H-Inp-D-1-Nal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO:  145)H-Inp-D-1-Nal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO:  145)H-Inp-D-1-Nal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO:  146)H-Inp-D-1-Nal-D-Bal-Pff-NH₂; (SEQ ID NO:  145)H-Inp-D-1-Nal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO:  145)H-Inp-D-1-Nal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO:  146)H-Inp-D-1-Nal-D-Bal-Taz-NH₂; (SEQ ID NO:  147)H-Inp-D-1-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  116)H-Inp-D-1-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  147)H-Inp-D-1-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  147)H-Inp-D-1-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  116)H-Inp-D-1-Nal-D-Trp-Pff-NH₂; (SEQ ID NO:  116)H-Inp-D-1-Nal-D-Trp-Taz-NH₂; (SEQ ID NO:  148)H-Inp-D-2-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  148)H-Inp-D-2-Nal-D-Trp-2-Thi-Apc-NH₂; (SEQ ID NO:  148)H-Inp-D-2-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-3-Thi-NH₂; (SEQ ID NO:  148)H-Inp-D-2-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-Pff-NH₂; (SEQ ID NO:  135)H-Inp-D-2-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-Taz-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO:  150)H-Inp-D-Bal-D-Bal-2-Fua-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO:  150)H-Inp-D-Bal-D-Bal-Pff-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO:  150)H-Inp-D-Bal-D-Bal-Taz-NH₂; (SEQ ID NO:  151)H-Inp-D-Bal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  121)H-Inp-D-Bal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  152)H-Inp-D-Bal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  151)H-Inp-D-Bal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  121)H-Inp-D-Bal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  151)H-Inp-D-Bal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  121)H-Inp-D-Bal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  152)H-Inp-D-Bal-D-Trp-Pff-NH₂; (SEQ ID NO:  152) H-Inp-D-Bal-D-Trp-Taz-NH₂;(SEQ ID NO:  153) H-Inp-D-Bip-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO:  154)H-Inp-D-Bip-D-Bal-2-Fua-NH₂; (SEQ ID NO:  153)H-Inp-D-Bip-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO:  153)H-Inp-D-Bip-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO:  153)H-Inp-D-Bip-D-Bal-Pff-Lys-NH₂; (SEQ ID NO:  154)H-Inp-D-Bip-D-Bal-Pff-NH₂; or (SEQ ID NO:  153)H-Inp-D-Bip-D-Bal-Taz-Lys-NH₂; (SEQ ID NO:  154)H-Inp-D-Bip-D-Bal-Taz-NH₂; (SEQ ID NO:  155)H-Inp-D-Bip-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  156)H-Inp-D-Bip-D-Trp-2-Fua-NH₂; (SEQ ID NO:  155)H-Inp-D-Bip-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  155)H-Inp-D-Bip-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  155)H-Inp-D-Bip-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  156)H-Inp-D-Bip-D-Trp-Pff-NH₂; (SEQ ID NO:  155)H-Inp-D-Bip-D-Trp-Taz-Lys-NH₂; or (SEQ ID NO:  156)H-Inp-D-Bip-D-Trp-Taz-NH₂; (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-3-Pal-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-4-Pal-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-Orn-Lys-NH₂; (SEQ ID NO:  111)H-Inp-D-Bip-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-Thr(Bzl)-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  111)H-Inp-D-Dip-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  111)H-Inp-D-Bpa-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  114)H-Inp-D-2-Nal-D-Bpa-Phe-Lys-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-Thr(Bzl)-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-Pff-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-Taz-NH₂; (SEQ ID NO:  118)H-Inp-D-2-Nal-D-Dip-Phe-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-3-Pal-Lys-NH₂; (SEQ ID NO:  120)H-Inp-D-Trp-D-2-Nal(Ψ)-Pim; (SEQ ID NO:  121)H-Inp-D-Bal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  111)H-Inp-D-Bal-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  122)H-Inp-D-2-Nal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO:  122)H-Inp-D-1-Nal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO:  122)H-Inp-D-Bal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO:  123)H-Apc-D-2-Nal-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  124)H-Apc-D-1-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  126)H-Inp-D-2-Nal-D-Trp(Ψ)-Pim; (SEQ ID NO:  126)H-Inp-D-1-Nal-D-Trp(Ψ)-Pim; (SEQ ID NO:  126) H-Inp-D-Bal-D-Trp(Ψ)-Pim;(SEQ ID NO:  127) H-Aib-D-Ser(Bzl)-D-Trp(Ψ)-Pim; (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  121)H-Inp-D-Bal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  124)H-Apc-D-1-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  128)H-Apc-D-Bal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  128)H-Apc-D-Bal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  123)H-Apc-D-Bal-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  129)H-Apc-D-1-Nal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO:  130)H-Apc-D-Bal-D-Trp-Phe-Apc-NH₂; (SEQ ID NO:  129)H-Apc-D-1-Nal-D-1-Nal-Phe-Apc-NH₂; (SEQ ID NO:  129)H-Apc-D-1-Nal-D-2-Nal-Phe-Apc-NH₂; (SEQ ID NO:  131)H-Apc-D-1-Nal-D-1-Nal-Phe-Lys-NH₂; (SEQ ID NO:  130)H-Apc-D-Bal-D-1-Nal-Phe-Apc-NH₂; (SEQ ID NO:  130)H-Apc-D-Bal-D-2-Nal-Phe-Apc-NH₂; (SEQ ID NO:  132)H-Apc-D-Bal-D-1-Nal-Phe-Lys-NH₂; (SEQ ID NO:  132)H-Apc-D-Bal-D-2-Nal-Phe-Lys-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-2-Thi-NH₂; (SEQ ID NO:  157)H-Apc-D-Bal-D-Trp-Phe-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-Taz-NH₂; (SEQ ID NO:  157)H-Apc-D-Bal-D-Trp-2-Thi-NH₂; (SEQ ID NO:  157)H-Apc-D-Bal-D-Trp-Taz-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-2-Thi-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-Taz-NH₂; (SEQ ID NO:  135)H-Inp-D-1-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  135)H-Inp-D-Bal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  136)H-Apc-D-1-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  136)H-Apc-D-Bal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  113)H-Inp-D-2-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  121)H-Inp-D-Bal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  121)H-Inp-D-Bal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  121)H-Inp-D-Bal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  151)H-Inp-D-Bal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  151)H-Inp-D-Bal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  151)H-Inp-D-Bal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  128)H-Apc-D-Bal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  128)H-Apc-D-Bal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  128)H-Apc-D-Bal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO:  149)H-Inp-D-Bal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO:  132)H-Apc-D-Bal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO:  141)H-Apc-D-Bal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO:  141)H-Apc-D-Bal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO:  141)H-Apc-D-Bal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO:  141)H-Apc-D-Bal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO:  141)H-Apc-D-Bal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  112)H-Inp-D-1-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  158)H-Inp-D-1-Nal-D-Bal-Phe-Lys-NH₂; (SEQ ID NO:  158)H-Inp-D-1-Nal-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO:  158)H-Inp-D-1-Nal-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO:  158)H-Inp-D-1-Nal-D-Bal-Taz-Lys-NH₂; (SEQ ID NO:  158)H-Inp-D-1-Nal-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO:  158)H-Inp-D-1-Nal-D-Bal-Pff-Lys-NH₂; (SEQ ID NO:  159)H-Inp-D-2-Nal-D-Trp-2-Thi-Apc-NH₂; (SEQ ID NO:  159)H-Inp-D-2-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  135)H-Inp-D-2-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  159)H-Inp-D-2-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  159)H-Inp-D-2-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  160)H-Inp-D-1-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  160)H-Inp-D-1-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  160)H-Inp-D-1-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  124)H-Apc-D-1-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  124)H-Apc-D-1-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  124)H-Apc-D-1-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  139)H-Apc-D-2-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  139)H-Apc-D-2-Nal-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  139)H-Apc-D-2-Nal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  139)H-Apc-D-2-Nal-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  139)H-Apc-D-2-Nal-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  155)H-Inp-D-Bip-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO:  155)H-Inp-D-Bip-D-Trp-3-Thi-Lys-NH₂; (SEQ ID NO:  155)H-Inp-D-Bip-D-Trp-Taz-Lys-NH₂; (SEQ ID NO:  155)H-Inp-D-Bip-D-Trp-2-Fua-Lys-NH₂; (SEQ ID NO:  155)H-Inp-D-Bip-D-Trp-Pff-Lys-NH₂; (SEQ ID NO:  153)H-Inp-D-Bip-D-Bal-2-Thi-Lys-NH₂; (SEQ ID NO:  153)H-Inp-D-Bip-D-Bal-3-Thi-Lys-NH₂; (SEQ ID NO:  153)H-Inp-D-Bip-D-Bal-Taz-Lys-NH₂; (SEQ ID NO:  153)H-Inp-D-Bip-D-Bal-2-Fua-Lys-NH₂; (SEQ ID NO:  153)H-Inp-D-Bip-D-Bal-Pff-Lys-NH₂; (SEQ ID NO:  143)H-Apc-D-Bal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  143)H-Apc-D-Bal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  143)H-Apc-D-Bal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  130)H-Apc-D-Bal-D-Bal-Phe-Apc-NH₂; (SEQ ID NO:  140)H-Apc-D-Bal-D-Bal-2-Thi-Apc-NH₂; (SEQ ID NO:  140)H-Apc-D-Bal-D-Bal-3-Thi-Apc-NH₂; (SEQ ID NO:  140)H-Apc-D-Bal-D-Bal-Taz-Apc-NH₂; (SEQ ID NO:  140)H-Apc-D-Bal-D-Bal-2-Fua-Apc-NH₂; (SEQ ID NO:  140)H-Apc-D-Bal-D-Bal-Pff-Apc-NH₂; (SEQ ID NO:  137)H-Apc-D-1-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  137)H-Apc-D-1-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  137)H-Apc-D-1-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  138)H-Apc-D-2-Nal-D-Trp-2-Thi-Apc-NH₂; (SEQ ID NO:  138)H-Apc-D-2-Nal-D-Trp-3-Thi-Apc-NH₂; (SEQ ID NO:  136)H-Apc-D-2-Nal-D-Trp-Taz-Apc-NH₂; (SEQ ID NO:  138)H-Apc-D-2-Nal-D-Trp-2-Fua-Apc-NH₂; (SEQ ID NO:  138)H-Apc-D-2-Nal-D-Trp-Pff-Apc-NH₂; (SEQ ID NO:  152)H-Inp-D-Bal-D-Trp-Taz-NH₂; (SEQ ID NO:  152)H-Inp-D-Bal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  152)H-Inp-D-Bal-D-Trp-Pff-NH₂; (SEQ ID NO:  157)H-Apc-D-Bal-D-Trp-3-Thi-NH₂; (SEQ ID NO:  157)H-Apc-D-Bal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  157)H-Apc-D-Bal-D-Trp-Pff-NH₂; (SEQ ID NO:  157)H-Apc-D-Bal-D-Trp-4-Pal-NH₂; (SEQ ID NO:  157)H-Apc-D-Bal-D-Trp-3-Pal-NH₂; (SEQ ID NO:  157)H-Apc-D-Bal-D-Trp-2-Pal-NH₂; (SEQ ID NO:  150)H-Inp-D-Bal-D-Bal-Taz-NH₂; (SEQ ID NO:  150)H-Inp-D-Bal-D-Bal-2-Fua-NH₂; (SEQ ID NO:  150)H-Inp-D-Bal-D-Bal-Pff-NH₂; (SEQ ID NO:  142) H-Apc-D-Bal-D-Bal-Phe-NH₂;(SEQ ID NO:  142) H-Apc-D-Bal-D-Bal-2-Thi-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-3-Thi-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-Taz-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-2-Fua-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-Pff-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-4-Pal-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-3-Pal-NH₂; (SEQ ID NO:  142)H-Apc-D-Bal-D-Bal-2-Pal-NH₂; (SEQ ID NO:  116)H-Inp-D-1-Nal-D-Trp-Taz-NH₂; (SEQ ID NO:  116)H-Inp-D-1-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  116)H-Inp-D-1-Nal-D-Trp-Pff-NH₂; (SEQ ID NO:  161)H-Inp-D-1-Nal-D-Bal-Taz-NH₂; (SEQ ID NO:  161)H-Inp-D-1-Nal-D-Bal-2-Fua-NH₂; (SEQ ID NO:  161)H-Inp-D-1-Nal-D-Bal-Pff-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-Taz-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  115)H-Inp-D-2-Nal-D-Trp-Pff-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-3-Thi-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-Pff-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-4-Pal-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-3-Pal-NH₂; (SEQ ID NO:  133)H-Apc-D-1-Nal-D-Trp-2-Pal-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-3-Thi-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-2-Fua-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-Pff-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-4-Pal-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-3-Pal-NH₂; (SEQ ID NO:  134)H-Apc-D-2-Nal-D-Trp-2-Pal-NH₂; (SEQ ID NO:  156)H-Inp-D-Bip-D-Trp-Taz-NH₂; (SEQ ID NO:  156)H-Inp-D-Bip-D-Trp-2-Fua-NH₂; (SEQ ID NO:  156)H-Inp-D-Bip-D-Trp-Pff-NH₂; (SEQ ID NO:  154) H-Inp-D-Bip-D-Bal-Taz-NH₂;(SEQ ID NO:  154) H-Inp-D-Bip-D-Bal-2-Fua-NH₂; or (SEQ ID NO:  154)H-Inp-D-Bip-D-Bal-Pff-NH₂; (SEQ ID NO:  147)H-Inp-D-1-Nal-D-Trp-2-Thi-Apc-N_(H2); (SEQ ID NO:  151)H-Inp-D-Bal-D-Trp-2-Thi-Apc-NH₂; (SEQ ID NO:  137)H-Apc-D-1-Nal-D-Trp-2-Thi-Apc-NH₂; (SEQ ID NO:  143)H-Apc-D-Bal-D-Trp-2-Thi-Apc-NH₂; or (SEQ ID NO:  131)H-Apc-D-1-Nal-D-Trp-Phe-Lys-NH₂; (SEQ ID NO:  162)(Ser(n-octanoyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  163)(Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  164)(Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂; (SEQ ID NO:  165)(Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  166)(Aib², Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  167)(Aib², Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂; (SEQ ID NO:  168)(Aib^(2,8), Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  169)(Aib^(2,8), Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂; (SEQ ID NO:  170)(Aib^(2,10), Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂; (SEQ ID NO:  171)(Aib^(2,10), Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂; (SEQ ID NO:  172)(Ser(n-octanoyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  173)(Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  174)(Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂; (SEQ ID NO:  175)(Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  176)(Aib², Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  177)(Aib², Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂; (SEQ ID NO:  178)(Aib^(2,8), Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  179)(Aib^(2,8), Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂; (SEQ ID NO:  180)(Aib^(2,10), Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂; (SEQ ID NO:  181)(Aib^(2,10), Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂; (SEQ ID NO:  182)(Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  183)(Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  184)(Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂; (SEQ ID NO:  185)(Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  186)(Dap(octanesulfonyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  187)(Dap(octanesulfonyl)^(3,17))hGhrelin(1-28)-NH₂; (SEQ ID NO:  188)(Dap(octanesulfonyl)³, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  189)(Dap(octanesulfonyl)³, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  190)(Glu(NH-hexyl)³, Dap(octanesulfonyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  191) (Cys(S-(CH₂)₉CH₃)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  192) (Cys(S-(CH₂)₉CH₃)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  193)(Glu(NH-hexyl)³, Cys(S-(CH₂)₉CH₃)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  194)(Cys(S-(CH₂)₉CH₃)3, Glu(NH-hexyl)17)hGhrelin(1-28)-NH₂;(SEQ ID NO:  195)(Cys(S-(CH₂)₉CH₃)3, Ser(n-octanoyl)17)hGhrelin(1-28)-NH₂;(SEQ ID NO:  196) (Aib², Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  197) (Aib², Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  198) (Aib², Thz⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  198) (Aib², 4-Hyp⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  198) (Aib², Dhp⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  198) (Aib², Pip⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  198) (Aib², Tic⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  199) (Aib², Glu(NH-hexyl)^(3,17), Thz⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  200)(Aib², Glu(NH-hexyl)^(3,17), 4-Hyp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  200) (Aib², Glu(NH-hexyl)^(3,17), Dhp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  200) (Aib², Glu(NH-hexyl)^(3,17), Pip⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  200) (Aib², Glu(NH-hexyl)^(3,17), Tic⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  201) (Aib^(2,8), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  202) (Aib^(2,8), Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  203) (Aib², 3-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  203) (Aib², 4-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  203) (Aib², Taz⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  203) (Aib², 2-Thi⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  204)(Aib², Glu(NH-hexyl)^(3,17), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  204)(Aib², Glu(NH-hexyl)^(3,17), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  204) (Aib², Glu(NH-hexyl)^(3,17), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  204)(Aib², Glu(NH-hexyl)^(3,17), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  205) (Aib^(2,10), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  206) (Aib^(2,10), Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  207) (Aib⁸, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  208) (Taz⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  208) (3-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  208) (4-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  208) (2-Thi⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  209) (Glu(NH-hexyl)^(3,17), Aib⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO:  210) (Glu(NH-hexyl)^(3,17), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  210) (Glu(NH-hexyl)^(3,17), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  210) (Glu(NH-hexyl)^(3,17), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  210) (Glu(NH-hexyl)^(3,17), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  211) (Aib^(1,2,10), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  212)(Aib^(1,2,10), Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  196) (A5c², Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  197) (A5c², Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  184) (Glu(1-heptanol)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  213) (Asp(1-heptanol)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  184) (Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  213) (Asp(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  197) (Aib², Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  214) (Lys(biotinyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  215)(Ser(n-octanoyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO:  216)(Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO:  217)(Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂; (SEQ ID NO:  218)(Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO:  219)(Aib², Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO:  220)(Aib², Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂; (SEQ ID NO:  221)(Aib^(2,8), Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO:  222)(Aib^(2,8), Glu(NH-hexyl)^(3,)18)hGhrelin(1-28)-NH₂; (SEQ ID NO:  223)(Aib^(2,10), Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂; (SEQ ID NO:  224)(Aib^(2,10), Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂; (SEQ ID NO:  225)(Ser(n-octanoyl)¹⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  226)(Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  227)(Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂; (SEQ ID NO:  228)(Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  229)(Aib², Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  230)(Aib², Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂; (SEQ ID NO:  231)(Aib^(2,8), Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂;  (SEQ ID NO:  232)(Aib^(2,8), Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂; (SEQ ID NO:  233)(Aib^(2,10), Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  234)(Aib^(2,10), Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂; (SEQ ID NO:  235)(Ser(n-octanoyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO:  236)(Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO:  237)(Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂; (SEQ ID NO:  238)(Glu(NH-hexyl)³, Ser(n-octanoyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO:  239)(Aib², Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO:  240)(Aib², Glu(NH-hexyl)3^(,20))hGhrelin(1-28)-NH₂; (SEQ ID NO:  241)(Aib^(2,8), Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO:  242)(Aib^(2,8), Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂; (SEQ ID NO:  243)(Aib^(2,10), Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂; (SEQ ID NO:  244)(Aib^(2,10), Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂; (SEQ ID NO:  245)(Ac-Gly¹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  246)(Ac-Gly¹, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂; (SEQ ID NO:  247)(Ac-Gly¹, Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂; (SEQ ID NO:  248)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  249) (Ac-Gly¹, Dap(octanesulfonyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  250)(Ac-Gly¹, Dap(octanesulfonyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  251)(Ac-Gly¹, Dap(octanesulfonyl)³, Glu(NH-Hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  252)(Ac-Gly¹, Dap(octanesulfonyl)³, Ser(n-Octanoyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  253)(Ac-Gly¹, Glu(NH-hexyl)³, Dap(octanesulfonyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  254) (Ac-Gly¹, Cys(S-(CH2)9CH3)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  255) (Ac-Gly¹, Cys(S-(CH2)9CH3)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  256)(Ac-Gly¹, Glu(NH-hexyl)³, Cys(S-(CH2)9CH3)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  257)(Ac-Gly¹, Cys(S-(CH₂)₉CH₃)³, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  258)(Ac-Gly¹, Cys(S-(CH₂)₉CH₃)³, Ser(n-octanoyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  259) (Ac-Gly¹, Aib², Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  260)(Ac-Gly¹, Aib², Thz⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  260)(Ac-Gly¹, Aib², 4-Hyp⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  260)(Ac-Gly¹, Aib², Dhp⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  260)(Ac-Gly¹, Aib², Pip⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  260)(Ac-Gly¹, Aib², Tic⁷, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  261)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), Thz⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  261)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), 4-Hyp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  261)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), Dhp⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  261)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), Pip⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  261)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), Tic⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  262)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  263)(Ac-Gly¹, Aib², 3-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  263)(Ac-Gly¹, Aib², 4-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  263)(Ac-Gly¹, Aib², Taz⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  263)(Ac-Gly¹, Aib², 2-Thi⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  264)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  264)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  264)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  264)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,17), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  265)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  266)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  267) (Ac-Gly¹, Aib¹, Glu(NH-hexyl)^(l7))hGhrelin(1-28)-NH₂;(SEQ ID NO:  268) (Ac-Gly¹, Taz⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  268) (Ac-Gly¹, 3-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  268) (Ac-Gly¹, 4-Pal⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  268) (Ac-Gly¹, 2-Thi⁹, Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  269)(Ac-Gly¹, Glu(NH-hexyl)^(3,17), Aib⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO:  270)(Ac-Gly¹, Glu(NH-hexyl)^(3,17), Taz⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  270)(Ac-Gly¹, Glu(NH-hexyl)^(3,17), 3-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  270)(Ac-Gly¹, Glu(NH-hexyl)^(3,17), 4-Pal⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  270)(Ac-Gly¹, Glu(NH-hexyl)^(3,17), 2-Thi⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  271)(Ac-Aib¹, Aib^(2,10), Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  272)(Ac-Aib¹, Aib^(2,10), Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  259) (Ac-Gly¹, A5c², Glu(NH-hexyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  273)(Ac-Gly¹, A5c², Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  247) (Ac-Gly¹, Glu(1-heptanol)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  274) (Ac-Gly¹, Asp(1-heptanol)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  247) (Ac-Gly¹, Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  274) (Ac-Gly¹, Asp(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂;(SEQ ID NO:  275)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)³, Lys(biotinyl)¹⁷)hGhrelin(1-28)-NH₂;(SEQ ID NO:  276) (Ac-Gly¹, Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  277) (Ac-Gly¹, Ser(n-octanoyl)¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  278) (Ac-Gly¹, Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂;(SEQ ID NO:  279)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  280) (Ac-Gly¹, Aib², Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  281)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂;(SEQ ID NO:  282)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  283)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂;(SEQ ID NO:  284)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)¹⁵)hGhrelin(1-28)-NH₂;(SEQ ID NO:  285)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,15))hGhrelin(1-28)-NH₂;(SEQ ID NO:  286) (Ac-Gly¹, Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  287) (Ac-Gly¹, Ser(n-octanoyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  288) (Ac-Gly¹, Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂;(SEQ ID NO:  289)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  290) (Ac-Gly¹, Aib², Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  291)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂;(SEQ ID NO:  292)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  293)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂;(SEQ ID NO:  294)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)¹⁶)hGhrelin(1-28)-NH₂;(SEQ ID NO:  295)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,16))hGhrelin(1-28)-NH₂;(SEQ ID NO:  296) (Ac-Gly¹, Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO:  297) (Ac-Gly¹, Ser(n-octanoyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO:  298) (Ac-Gly¹, Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂;(SEQ ID NO:  299)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO:  300) (Ac-Gly¹, Aib², Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO:  301)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂;(SEQ ID NO:  302)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO:  303)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂;(SEQ ID NO:  304)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)¹⁸)hGhrelin(1-28)-NH₂;(SEQ ID NO:  305)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,18))hGhrelin(1-28)-NH₂;(SEQ ID NO:  306) (Ac-Gly¹, Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  307) (Ac-Gly¹, Ser(n-octanoyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  308) (Ac-Gly¹, Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂;(SEQ ID NO:  309)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  310) (Ac-Gly¹, Aib², Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  311)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂;(SEQ ID NO:  312)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  313)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂;(SEQ ID NO:  314)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)¹⁹)hGhrelin(1-28)-NH₂;(SEQ ID NO:  315)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,19))hGhrelin(1-28)-NH₂;(SEQ ID NO:  316) (Ac-Gly¹, Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO:  317) (Ac-Gly¹, Ser(n-octanoyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO:  318) (Ac-Gly¹, Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂;(SEQ ID NO:  319)(Ac-Gly¹, Glu(NH-hexyl)³, Ser(n-octanoyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO:  320) (Ac-Gly¹, Aib², Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO:  321)(Ac-Gly¹, Aib², Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂;(SEQ ID NO:  322)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO:  323)(Ac-Gly¹, Aib^(2,8), Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂;(SEQ ID NO:  324)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)²⁰)hGhrelin(1-28)-NH₂;(SEQ ID NO:  325)(Ac-Gly¹, Aib^(2,10), Glu(NH-hexyl)^(3,20))hGhrelin(1-28)-NH₂;(SEQ ID NO:  326) (Asp³(NH-heptyl))hGhrelin(1-28)-NH₂ Example #86(SEQ ID NO:  327) (des-Ser²)hGhrelin(1-28)-NH₂; Example #104 or(SEQ ID NO:  328) (des-Gly¹, des-Ser²)hGhrelin(1-28)-NH₂; Example #117(SEQ ID NO:  329) (Aib¹)hGhrelin(1-28)-NH₂; Example #6 (SEQ ID NO:  326)(Asp³(O-hexyl))hGhrelin(1-28)-NH₂; Example #40 (SEQ ID NO:  329)(Aib¹, Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  3)(A5c⁵, Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  330)(Aib^(2,4), Ser³, 4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  95)(n-octanoyl-Gly¹, Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  95)(isobutyryl-Gly¹, Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  95)(n-butyryl-Gly¹, Ser³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  331)(Aib¹, Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  330)(Aib^(2,4), Thr³, 4-Pal⁹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  332)(n-octanoyl-Gly¹, Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  332)(isobutyryl-Gly¹, Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  332)(n-butyryl-Gly¹, Thr³)hGhrelin(1-28)-NH₂; (SEQ ID NO:  95)(Ac-Gly¹)hGhrelin(1-28)-NH₂; (SEQ ID NO:  95)(Ac-Gly¹, Ser³)hGhrelin(1-28)-NH₂, (SEQ ID NO:  333)Aib², Lys(Myristyl)¹⁷)hGhrelin-(1-28)-NH₂; or (SEQ ID NO:  334)Gly(myristyl)¹-(Aib², Lys(Myristyl)¹⁷]hGhrelin-(1-28)-NH₂;

The present invention includes diastereomers as well as their racemicand resolved enantiomerically pure forms. Ghrelin analogs can containD-amino acids, L-amino acids or a combination thereof. Preferably, aminoacids present in a ghrelin analog are the L-enantiomers.

Preferred derivatives of analogs of the invention comprise D-aminoacids, N-alkyl-amino acids, β-amino acids and/or one or more labeledamino acids (including a labeled version of a D-amino acid,N-alkyl-amino acids, or a β-amino acid). A labeled derivative indicatesthe alteration of an amino acid or amino acid derivative with adetectable label. Examples of detectable labels include luminescent,enzymatic and radioactive labels. Both the type of label and theposition of the label can affect analog activity. Labels should beselected and positioned so as not to substantially alter the activity ofthe ghrelin analog at the GHS receptor. The effect of a particular labeland position on ghrelin activity can be determined using assaysmeasuring ghrelin activity and/or binding.

A therapeutically effective amount depends upon the condition beingtreated, the route of administration chosen, and the specific activityof the compound used and ultimately will be decided by the attendingphysician or veterinarian (e.g., between 5 g/day to 5 mg/day). In oneembodiment, the peptidyl analog of ghrelin is administered to thepatient until the symptoms associated with gastrointestinal dysmotility,for example the abdominal nausea, distension, vomiting, obstipation,inability to eat and cramps often associated with postoperative ileus,observed in patient have been alleviated or ceased.

The ileus treatable by the method of the invention can be ileus of anyportion of the gastrointestinal tract, e.g., the stomach, smallintestine and/or the colon. The ileus can result from any factor thatcauses ileus, e.g., surgery, e.g., abdominal surgery such astransplantation surgery (e.g., small intestinal transplantation (SITx))or abdominal surgery other than transplantation surgery (e.g., abdominalsurgery involving laparotomy or not involving laparotomy, e.g.,laproscopic procedures); orthopedic surgeries (e.g., hip surgery);parturition; intestinal ischaemia; retroperitoneal haematoma;intraabdominal sepsis; intraperitoneal inflammation, e.g., acuteappendicitis, choecystitis, pancreatitis; fractures of the spine;ureteric colic; thoracic lesions; basal pneumonia; rib fractures;myocardial infarction; metabolic disturbances; or any combinationthereof.

The peptidyl analog of ghrelin may be injected parenterally, e.g.,intravenously, into the bloodstream of the subject being treated,however, it will be readily appreciated by those skilled in the art thatthe route, such as intravenous, subcutaneous, intramuscular,intraperitoneal, enterally, transdermally, transmucously, sustainedreleased polymer compositions (e.g., a lactic acid polymer or copolymermicroparticle or implant), profusion, nasal, oral, etc., will vary withthe condition being treated and the activity and bioavailability of thepeptidyl analog of ghrelin being used.

While it is possible for the peptidyl analog of ghrelin to beadministered as the pure or substantially pure compound, it may also bepresented as a pharmaceutical formulation or preparation. Theformulations to be used in the present invention, for both humans andanimals, comprise any of the peptidyl analog of ghrelin to be describedbelow, together with one or more pharmaceutically acceptable carriersthereof, and optionally other therapeutic ingredients.

The carrier must be “acceptable” in the sense of being compatible withthe active ingredient(s) of the formulation (e.g., capable ofstabilizing peptides) and not deleterious to the subject to be treated.Desirably, the formulation should not include oxidizing agents or othersubstances with which peptides are known to be incompatible. Highlyoxidative conditions can lead to the formation of cysteine sulfoxide andto the oxidation of tryptophan. Consequently, it is important tocarefully select the excipient.

The pharmaceutical formulation can be administered to the patient by anymethod known in the art for administering gases, liquids, and/or solidsto patients, e.g., via inhalation, insufflation, infusion, injection,and/or ingestion. For example, in one embodiment of the presentinvention, the pharmaceutical composition is administered to the patientby inhalation. In another embodiment, the pharmaceutical composition isadministered to the patient orally. In yet another embodiment, thepharmaceutical composition is administered directly to the abdominalcavity of the patient.

The formulations may conveniently be presented in unit dosage form andmay be prepared by any of the methods well known in the art of pharmacy.All methods include the step of bringing the active ingredient(s) intoassociation with the carrier which constitutes one or more accessoryingredients.

In general, the formulations for tablets or powders are prepared byuniformly and intimately blending the active ingredient with finelydivided solid carriers, and then, if necessary, as in the case oftablets, forming the product into the desired shape and size.

Formulations suitable for parenteral (e.g., intravenous) administration,on the other hand, conveniently comprise sterile aqueous solutions ofthe active ingredient(s). Preferably, the solutions are isotonic withthe blood of the subject to be treated. Such formulations may beconveniently prepared by dissolving solid active ingredient(s) in waterto produce an aqueous solution, and rendering said solution sterile. Theformulation may be presented in unit or multi-dose containers, forexample, sealed ampoules or vials.

Formulations suitable for sustained release parenteral administrations(e.g., biodegradable polymer formulations such as polyesters containinglactic or glycolic acid residues) are also well known in the art (see,e.g., U.S. Pat. Nos. 3,773,919 and 4,767,628 and PCT Publication WO94/15587).

In addition to treating postoperative ileus, patients suffering fromileus undergoing the method of the instant application also benefit fromother known therapeutic effects of ghrelin such as orexigenic effects,inhibition of inflammatory cytokines, promotion of slow wave sleep andimmune enhancing properties.

Examples A. Synthesis of Ghrelin Analogs

The ghrelin analogues and compounds of the invention can be producedusing the techniques disclosed in the examples herein as well astechniques that are well known in the art. For example, a polypeptideregion of a ghrelin analog can be chemically or biochemicallysynthesized and modified. Examples of techniques for biochemicalsynthesis involving the introduction of a nucleic acid into a cell andexpression of nucleic acids are provided in Ausubel, Current Protocolsin Molecular Biology, John Wiley, 1987-1998 and Sambrook et al., inMolecular Cloning, A Laboratory Manual, 2^(nd) Edition, Cold SpringHarbor Laboratory Press, 1989. Techniques for chemical synthesis ofpolypeptides are also well known in the art (See e.g., Vincent inPeptide and Protein Drug Delivery, New York, N.Y., Dekker, 1990). Forexample, the peptides of this invention can be prepared by standardsolid phase peptide synthesis (See, e.g., Stewart, J. M., et al., SolidPhase Synthesis, Pierce Chemical Co., 2d ed. 1984).

The substituents R² and R³ of the above generic formula may be attachedto the free amine of the N-terminal amino acid by standard methods knownin the art. For example, alkyl groups, e.g., (C₁-C₃₀)alkyl, may beattached using reductive alkylation. Hydroxyalkyl groups, e.g.,(C₁-C₃₀)hydroxyalkyl, may also be attached using reductive alkylationwherein the free hydroxy group is protected with a t-butyl ester. Acylgroups, e.g., COE¹, may be attached by coupling the free acid, e.g.,E¹COOH, to the free amine of the N-terminal amino acid by mixing thecompleted resin with 3 molar equivalents of both the free acid anddiisopropylcarbodiimide in methylene chloride for 1 hour. If the freeacid contains a free hydroxy group, e.g., p-hydroxyphenylpropionic acid,then the coupling should be performed with an additional 3 molarequivalents of HOBT.

When R¹ is NH—X²—CH₂—CONH₂, (i.e., Z⁰═CONH₂), the synthesis of thepeptide starts with Fmoc-HN—X²—CH₂—COOH coupled to a Rink Amide-MBHAresin (Amide-4-methylbenzylhydryl amine obtained from Novabiochem®, SanDiego, Calif.). If R¹ is NH—X²—CH₂—COOH (i.e., Z⁰—COOH) the synthesis ofthe peptide starts with Fmoc-HN—X²—CH₂—COOH which is coupled to Wangresin.

In the synthesis of a ghrelin analogue of this invention containing A5c,A6c and/or Aib, the coupling time is 2 hours for these residues and theresidue immediately following them.

A protecting group covalently joined to the C-terminal carboxy groupreduces the reactivity of the carboxy terminus under in vivo conditions.The carboxy terminus protecting group is preferably attached to theα-carbonyl group of the last amino acid. Preferred carboxy terminusprotecting groups include amide, methylamide, and ethylamide.

Examples are provided below to further illustrate different features ofthe present invention. The examples also illustrate useful methodologyfor practicing the invention. These examples do not limit the claimedinvention.

Synthesis of short amino acid sequences is well established in thepeptide art. For example, synthesis of compounds according to formula Isuch as (Glu³(O-hexyl))hGhrelin(1-28)-NH₂ (SEQ ID NO:1),(Aib²)hGhrelin(1-28)-NH₂ (SEQ ID NO:10),(Glu³(NH-hexyl))hGhrelin(1-28)-NH₂ (SEQ ID NO:1) and(Cys³(S-decyl))hGhrelin(1-28)-NH₂ (SEQ ID NO:1) described above, can beachieved by following the protocol set forth in International PatentPublication WO04/009616 at pages 46 to 56 at follows:

Example 1: (Glu³(O-Hexyl))hGhrelin(1-28)-NH₂ (SEQ ID NO:1)

The titled peptide was synthesized on an Applied Biosystems (FosterCity, Calif.) model 433A peptide synthesizer.4-(2′,4′-Dimethoxyphenyl-Fmoc-aminomethyl)-phenoxyacetamido-norleucyl-MBHAresin (Rink Amide MBHA resin, Novabiochem, San Diego, Calif.) was usedwith a substitution of 0.72 mmol/g. The Fmoc amino acids (AnaSpec, SanJose, Calif.) were used with the following side chain protection:Fmoc-Arg(Pbf)-OH, Fmoc-Pro-OH, Fmoc-Gln-OH, Fmoc-Leu-OH,Fmoc-Lys(Boc)-OH, Fmoc-Ala-OH, Fmoc-Ser(tBu)-OH, Fmoc-Glu(OtBu)-OH,Fmoc-Val-OH, Fmoc-His(Trt)-OH, Fmoc-Phe-OH, and Fmoc-Asp(OtBu)-OH.Boc-Gly-OH (Midwest Bio-Tech, Fishers, Ind.) was used in position 1.N-α-Fmoc-L-glutamic acidγ-4-{N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl)-amino}benzyl ester (Fmoc-Glu(ODmab)-OH) (Chem-Inpex International, Wood Dale,Ill.) was used in position 3. The synthesis was carried out on a 0.25mmol scale. The Fmoc groups were removed by treatment with 20%piperidine in N-methylpyrrolidone (NMP) for 30 min. In each couplingstep, the Fmoc amino acid (1 mmol) was first pre-activated with HBTU(0.9 mmol) and HOBt (0.9 mmol) in DMF and then added to the resin. TheABI 433A peptide synthesizer was programmed to perform the followingreaction cycle: (1) washing with NMP, (2) removing Fmoc protecting groupwith 20% piperidine in NMP for 30 min, (3) washing with NMP, (4)coupling with pre-activated Fmoc amino acid for 1 h.

At the end of assembly of the peptide chain on the Applied Biosystems(ABI) 433A peptide synthesizer, the resin was transferred into areaction vessel on a shaker for manual synthesis. The Dmab protectinggroup in the side chain of the Glu residue was removed with a solutionof 2% hydrazine in DMF for 2 h. After washing with DMF, the resin wastreated with 2.5 mmol of tetramethylfluoroforamidiniumhexafluorophosphate (TFFH) (Perseptive Biosystems, Warrington, UK) indichloromethane (DCM) for 25 min to convert the free carboxylic acidfunctional group in the side chain of the Glu residue to its acidfluoride. To the mixture were added 5.0 mmol of hexanol, 2.5 mmol ofO-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HOAT)(Anaspec, San Jose, Calif.), 5.0 mmol ofdiisopropylethyl amine (DIEA)(Aldrich, Milwaukee, Wis.) and catalyticamount of 4-(dimethylamino)pyridine (DMAP)(Aldrich, Milwaukee, Wis.).The mixture was shaken at room temperature for 2 h. The resin was washedwith DMF and DCM and treated overnight with 2.5 mmol of N,N-diisopropylcarbodiimide (DIC)(Chem-Impex International, Wood Dale,Ill.), 2.5 mmol of 1-hexanol, 2.5 mmol of HOBt, and 0.025 mmol of DMAP.After washing and drying, the peptide was cleaved off from the resin byusing a mixture of TFA (9.5 mL), H₂O (0.85 mL) and triisopropylsilane(TIS) (0.85 mL) for 2 h. The resin was filtered off and the filtrate waspoured into 70 mL of ether. The precipitate formed was filtered off andwashed thoroughly with ether. This crude product was dissolved into 5%acetic acid and purified on a reverse-phase preparative HPLC using acolumn (4×43 cm) of C₁₈ DYNAMAX-100A⁰ (Varian, Walnut Creek, Calif.).The column was eluted with a linear gradient from 75% A and 25% B to 55%A and 45% B in an hour where A was 0.1% TFA in water and B was 0.1% TFAin acetonitrile. The fractions were checked by an analytical HPLC. Thosecontaining pure product were combined and lyophilized to dryness. Thepurity of the compound was 92.8%. Yield was 8.6%. Electro-sprayionization mass spectrometry (ESI MS) analysis gave a molecular weightfor the product of 3369.4 (in agreement with the calculated molecularweight of 3369.9).

Example 2: (Aib²)hGhrelin(1-28)-NH₂ (SEQ ID NO:10)

The titled peptide was synthesized according to the procedure describedin Example 1 for the synthesis of (G100-Hexyl))hGhrelin(1-28)-NH₂ (SEQID NO:1), except as follows: Fmoc-Ser-OH was used at position 3,Fmoc-Aib-OH was used at position 2 and Boc-Gly-OH was used atposition 1. After the peptide chain was assembled, the peptide-resin wastreated with 25% piperidine in DMF for 3×2 h. The resin was washed withDMF and treated with octanoic acid (2.5 mmol, 10 fold excess), HBTU (2.2mmol), HOBt (2.2 mmol) and DIEA (7.5 mmol) in DMF for 2 h. The resin waswashed with DMF and then treated with octanoic acid (2.5 mmol), DIC (2.5mmol), HOBt (2.5 mmol) and DMAP (0.025 mmol) in DMF for 2 h. The finalcleavage and purification procedures were the same as those inExample 1. The product was found to be homogenous by analytical HPLC,with a purity of 99% in 18.5% yield. Electro-spray ionization massspectrometry (ESI MS) analysis gave a molecular weight for the productof 3367.6 (in agreement with the calculated molecular weight of 3367.0).

Example 3: (Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂ (SEQ ID NO:1)

The titled peptide was synthesized on an Applied Biosystems (FosterCity, Calif.) model 430A peptide synthesizer which was modified to doaccelerated Boc-chemistry solid phase peptide synthesis. See Schnolzer,et al., Int. J. Peptide Protein Res., 40:180 (1992).4-Methylbenzhydrylamine (MBHA) resin (Peninsula, Belmont, Calif.), witha substitution of 0.91 mmol/g was used. Boc amino acids (MidwestBio-Tech, Fishers, Ind.; Novabiochem., San Diego, Calif.) were used withthe following side chain protection: Boc-Ala-OH, Boc-Arg(Tos)-OH,Boc-His(DNP)—OH, Boc-Val-OH, Boc-Leu-OH, Boc-Gly-OH, Boc-Gln-OH,Boc-Lys(2ClZ)—OH, Boc-Ser(Bzl)-OH, Boc-Phe-OH, Boc-Glu(OcHex)-OH andBoc-Pro-OH. Fmoc-Glu(OtBu)-OH (Novabiochem., San Diego, Calif.) was usedfor the residue at position 3 in the sequence. The synthesis was carriedout on a 0.25 mmol scale. The Boc groups were removed by treatment with100% TFA for 2×1 min. Boc amino acids (2.5 mmol) were pre-activated withHBTU (2.0 mmol) and DIEA (1.0 mL) in 4 mL of DMF and were coupledwithout prior neutralization of the peptide-resin TFA salt. Couplingtimes were 5 min.

At the end of the assembly of the first 25 residues on the ABI 430Apeptide synthesizer and before the coupling of Fmoc-Glu(OtBu)-OH, theprotected peptide-resin was transferred into a reaction vessel on ashaker for manual synthesis. After removing the Boc protecting group byusing 100% TFA for 2×1 min and washing with DMF, the resin was mixedwith Fmoc-Glu(OtBu)-OH (2.5 mmol) which was pre-activated with HBTU (2.0mmol), HOBt (2.0 mmol) and DIEA (1.0 mL) in 4 mL of DMF. The mixture wasshaken for 2 h. This coupling step was repeated. After washing with DMF,the resin was treated with a TFA solution containing 5% water and 5% TISfor 2 h to remove the tBu protecting group in the side chain of the Gluresidue. The resin was neutralized with 10% DIEA in DMF and washed withDMF and DCM. The resin was then treated with hexylamine (2.0 mmol), DIC(2.0 mmol), HOBt (2.0 mmol) in 5 ml of DCM for 2×2 h. The resin waswashed with DMF and treated with 25% piperidine in DMF for 30 min toremove the Fmoc protecting group. After washing with DMF and DCM, theresin was transferred into the reaction vessel on the ABI 430A peptidesynthesizer for the assembly of the rest two residues.

At the end of the assembly of the whole peptide chain, the resin wastreated with a solution of 20% mercaptoethanol/10% DIEA in DMF for 2×30min to remove the DNP group on the His side chain. The N-terminal Bocgroup was then removed by treatment with 100% TFA for 2×2 min. Thepeptide-resin was washed with DMF and DCM and dried under reducedpressure. The final cleavage was done by stirring the peptide-resin in10 mL of HF containing 1 mL of anisole and dithiothreitol (50 mg) at 0°C. for 75 min. HF was removed by a flow of nitrogen. The residue waswashed with ether (6×10 mL) and extracted with 4N HOAc (6×10 mL). Thiscrude product was purified on a reverse-phase preparative HPLC using acolumn (4×43 cm) of C₁₈ DYNAMAX-100A⁰ (Varian, Walnut Creek, Calif.).The column was eluted with a linear gradient from 75% A and 25% B to 55%A and 45% B at flow rate of 10 mL/min in an hour where A was 0.1% TFA inwater and B was 0.1% TFA in acetonitrile. Fractions were collected andchecked on an analytical HPLC. Those containing pure product werecombined and lyophilized to dryness. 31.8 mg of a white solid wereobtained. Purity was 89% based on analytical HPLC analysis.Electro-spray ionization mass spectrometry (ESI MS) analysis gave themolecular weight at 3368.4 (in agreement with the calculated molecularweight of 3368.9).

Example 4: (Cys³(S-Decyl))hGhrelin(1-28)-NH₂ (SEQ ID NO:1)

(i) The titled peptide was synthesized according to the proceduredescribed in Example 3 for the synthesis of(Glu³(NH-Hexyl))hGhrelin(1-28)-NH₂ (SEQ ID NO:1) with the followingmodifications: After the assembly of the first 25 residues using Bocchemistry, the last 3 residues were assembled by employing Fmocchemistry. The following 3 Fmoc amino acids were used:N-α-Fmoc-S-(p-methoxytrityl)-L-cysteine (Fmoc-Cys(Mmt)-OH),Fmoc-Ser(Bzl)-OH and Fmoc-Gly-OH, which were purchased from Novabiochem(San Diego, Calif.). The Fmoc amino acid (1 mmol) was firstpre-activated with HBTU (0.9 mmol) and HOBt (0.9 mmol) in DMF before itwas coupled to the peptide-resin. The synthesis cycle for the Fmoc aminoacids included: (1) washing with NMP, (2) removing Fmoc protecting groupwith 20% piperidine in NMP for 30 min, (3) washing with NMP, and (4)coupling with pre-activated Fmoc amino acid for 1 h.

(ii) At the end of the assembly of the entire peptide chain, theprotected peptide-resin was treated with a solution of 20%mercaptoethanol and 10% DIEA in DMF for 2×30 min to remove the DNP groupon the side-chain of the His residue. The Mmt protecting group in theside-chain of the Cys residue was then removed by using a solution of 1%TFA and 5% TIS in DCM for 30 minutes and the peptide-resin was washedwith DMF.

(iii) 1-(2-pyridyldithio)decane was prepared by stirring 2, 2′-dipyridyldisulfide (1.06 g, 4.8 mmol), 1-decanethiol (0.83 mL, 4 mmol) andtriethylamine (2 mL) in propanol and acetonitrile (1/9, v/v) at roomtemperature for about 3 hours (See Carlsson et al., Biochem. J., 1978,173, 723-737). Purification of the crude 1-(2-pyridyldithio)decane wasperformed using flash chromatography, eluting with a mixed solventsystem of DCM/MeOH (10:0.4).

(iv) The peptide-resin from step (ii) was treated with the1-(2-pyridyldithio)decane from step (iii) and DIEA (3 eq., 0.75 mmol)overnight in a mixed solvent system of DMF/1-propanol (7:3). The resinwas then washed with DMF and the N-terminal Fmoc protecting group wasremoved by treatment with 25% piperidine in DMF for 30 min. Thepeptide-resin was then washed with DMF and DCM and dried under reducedpressure.

(v) Final cleavage was performed by stirring the peptide-resin in 10 mLof HF containing 1 mL anisole at about 0° C. for about 70 min. Thepurification procedure was the same as that described in Example 3. Thetarget product (yield 10.2%) was found by analytical HPLC to have apurity of 99.9%. Electro-spray ionization mass spectrometry (ESI-MS)analysis gave the molecular weight at 3432.1 (in agreement with thecalculated molecular weight of 3432.1).

Other peptides of the invention can be prepared by a person of ordinaryskill in the art using synthetic procedures analogous to those disclosedgenerally hereinabove in using the protocols set forth in InternationalPatent Publication WO04/009616. Other peptides of the invention can beprepared by a person of ordinary skill in the art using syntheticprocedures analogous to those disclosed generally hereinabove.

The synthesis of peptidyl analogs according to formula II, such asH-Inp-D-Bal-D-Trp-Phe-Apc-NH₂(SEQ ID NO:122), H-Inp-D-2-Nal-D-Trp(Ψ)-Pim(SEQ ID NO:126) and H-Inp-D-Trp-D-2-Nal(Ψ)-Pim (SEQ ID NO:120) can beachieved by following the protocol set forth in International PatentPublication WO04/014415 at pages 33-44 as follows:

Example 1: H-Apc-D-1-Nal-D-1-Nal-Phe-Apc-NH₂ (SEQ ID NO:129)

Each of the reaction wells contained 0.0675 mmol of Rink Amide MBHAresin (substitution=0.72 mmol/g, Novabiochem, San Diego, Calif.). Thefollowing Fmoc amino acids (Novabiochem, San Diego, Calif.; Chem-ImpexInternational, Wood Dale, Ill.; SyntheTech, Albany, Oreg.; Pharma Core,High Point, N.C.) were used: Fmoc-Lys(Boc)-OH, Fmoc-Phe-OH,Fmoc-H-Inp-OH, Fmoc-D-1-Nal-OH, Fmoc-D-2-Nal-OH, Fmoc-D-Trp(Boc)-OH,Fmoc-3-Pal-OH, Fmoc-4-Pal-OH, Fmoc-Orn(Boc)-OH, Fmoc-D-Bip-OH,Fmoc-Thr(Bzl)-OH, Fmoc-Pff-OH, Fmoc-2-Thi-OH, Fmoc-Taz-OH,Fmoc-D-Dip-OH, Fmoc-D-Bpa-OH, Fmoc-D-Bal-OH, and Fmoc-Apc(Boc)-OH.

Each of the Fmoc amino acids was dissolved in a 0.3 N solution of HOBtin DMF wherein the concentration of the resulting Fmoc amino acid was0.3 N. A four fold excess (0.27 mmol, 0.9 mL of the 0.3 N solution) ofFmoc amino acid was used for each coupling. DIC (0.27 mmol, 0.6 mL of0.45N DIC solution in DMF) was used as the coupling reagent for eachcoupling. Deprotection was performed by using 20% piperidine in DMF(2×1.5 mL per residue).

The peptides were cleaved from the resin by treating the peptide-resinswith 8% triisopropylsilane (TIP) in trifluoroacetic acid (TFA) (1.5 mLper reaction well) at room temperature for 2 h. The resin was removed byfiltration. Each filtrate was diluted to 25 mL with ether in acentrifuge tube. The resulting precipitate in each tube was centrifugedand the solvents were decanted from the precipitate. The precipitate ineach tube was then dissolved in methanol (3 mL) and diluted with water(1 mL). The purification of the crude products was done on areverse-phase preparative HPLC using a column (100×21.20 mm, 5μ) of LUNA5μ C₈(2) (Phenomenex, Torrance, Calif.). For each peptide, the columnwas eluted with a linear gradient from 85% A and 15% B to 25% A and 75%B in 15 min with a flow rate of 25 mL/min. A was 0.1% TFA in water and Bwas 0.1% TFA in acetonitrile/water (80/20, v/v). The fractions werechecked by analytical HPLC and those containing the pure product werecombined and lyophilized to dryness.

Yields ranged from 13% to 71% and purity of each of Examples 1-65exceeded 94% based upon analytical HPLC analysis. Electro-sprayionization mass spectrometry (ES-MS) analysis was performed and observedmolecular weights were in agreement with calculated molecular weights.The results are detailed in Table I, below.

Example 2: H-Inp-D-2-Nal-D-Trp(Ψ)-Pim (SEQ ID NO:126)

1.a. BOC-(D)-Trp-OH (4.0 g, 13.1 mmole) (Novabiochem San Diego, Calif.)in methanol (36 ml) and Cs₂CO₃ (2.14 g, 6.57 mmole) in water (10 ml)were combined and the mixture was swirled until a homogeneous mixturewas obtained. Solvents were removed in vacuo and the residue wasdissolved in DMF (45 ml). 2-bromoacetophenone (2.61 g, 13.1 mmole) inDMF (9 ml) was added to the solution and the solution was stirred for 30min. at room temperature. Cesium bromide was removed by filtration andthe filtrate was concentrated in vacuo. The resulting concentrate wasdissolved in xylenes (45 ml), NH₄OAc (17.1 g) was added, and thesolution was heated at reflux for 1 hr. The cooled solution was washedtwo times with saturated NaHCO₃ solution (45 ml) and then with saturatedNaCl. The resulting organic layer was purified by flash chromatographyto yield 4.1 g (77%) of intermediate 1A depicted in Scheme 1A,(“Compound 1A”).

1b. Compound 1A (403 mg) was deblocked using a mixture oftrifluoroacetic acid (TFA) (8 ml) dichloromethane (DCM) (8 ml) andtriisopropylsilane (TIPS) (1.4 ml). After mixing for one hour thesolution was concentrated under a stream of nitrogen. The residue wasdissolved in DCM (40 ml), washed two times with a saturated solution ofNaHCO₃(40 ml), and then dried over Na₂SO₄ to yield a solution of theintermediate product 1B, depicted in Scheme 1B, below.

1c.-f. The forgoing solution of the intermediate product 1B was dividedinto four equal portions and coupled with the pre-activated HOBT estersof FMOC protected amino acids, as summarized in reaction schemes 1C, 1D,1E, and 1F, below. The amino acid used: FMOC-D-2-Nal-OH (130 mg, 0.30mmole) (Synthetech Albany, Oreg.)

Each of the immediately foregoing amino acids was pre-activated withHOBT (46 mg, 0.30 mmole) and DIC (38 mg, 0.30 mmole) in DCM (5 ml) forten minutes before addition to one of the four portions of the forgoingsolution of the intermediate product 1B. The coupling reaction was thenallowed to proceed for 30 minutes at room temperature.

1.g-j. The FMOC group is removed from each of the resulting compounds1C, 1D, 1E and 1F by addition of tris(2-aminoethyl)amine (0.9 ml) to therespective reaction mixtures from the previous step and mixing for 30minutes at room temperature. The reaction mixtures containing thedeblocked compounds were then washed three times with 10% pH 5.5phosphate buffer (10 ml).

The resulting free amine solutions were coupled with pre-activated HOBTesters of FMOC-Inp-OH (105 mg, 0.30 mmole) (Chem Impex Wood Dale, Ill.)and was pre-activated with HOBT (46 mg, 0.30 mmole) and DIC (38 mg, 0.30mmole) in DCM (5 ml) for ten minutes before addition to the appropriatedeprotected amine. The coupling reaction was then allowed to proceed forone hour at room temperature.

The FMOC group was removed from the resulting FMOC-protected compoundsby addition of tris(2-aminoethyl)amine (0.9 ml) and mixing for 30minutes. The deblocked compounds were washed three times with 10% pH 5.5phosphate buffer (10 ml) and the crude products were collected as aprecipitate.

The BOC-protected compounds were purified by flash chromatography andthen deblocked for one hour with TIPS (0.50 ml), TFA (0.50 ml), in DCM(2.75 ml). The crude products were then concentrated and dried undervacuum.

The foregoing deprotection, coupling, and deprotection steps aresummarized in reaction schemes 1G, 1H, 1I and 1J, below

Example 3: H-Inp-D-Trp-D-2-Nal(Ψ)-Pim (SEQ ID NO:120)

2.a.1 and 2.a.2.: Compound 2A was made in an analogous manner as wasCompound 1A, using BOC-D-2-Nal-OH and 2-bromoacetophenone as startingmaterials.

Steps 2.a.1. and 2.a.2. are summarized in Scheme 2A, below.

2.b.1. Compound 2A (100 mg, 0.242 mmole) was deblocked in TFA (2 ml) andDCM (2 ml) for one hour. Volatiles were then removed under a stream ofnitrogen and the residue was dissolved in DCM (10 ml). The resultingsolution washed three times with saturated NaHCO₃(10 ml) to yield asolution of Compound 2A in free amine form.2.b.2. The active ester of FMOC-D-Trp-(BOC)—OH (153 mg, 0.290 mmole) waspreformed with N-hydroxysuccinimide (HOSu; 33 mg, 0.290 mmole) and DIC(37 mg, 0.290 mmole) in DCM (1.5 ml). After one hour diisopropylurea wasremoved by filtration and the filtrate was added to the Compound 2A(free amine) solution. The resulting solution was diluted with DCM to 4ml and the coupling reaction allowed to proceed for 30 minutes.

Steps 2.b.1. and 2.b.2. are summarized in Scheme 2B, below.

2.c.1 Compound 2B was deblocked by addition of tris(2-aminoethyl)amine(TAEA) (0.9 ml) to the immediately foregoing coupling reaction solutionand mixing for 30 minutes at room temperature. The reaction solution wasthen washed three times with saturated NaCl solution (10 ml) followed bythree times with 10% pH 5.5 phosphate buffer (10 ml) to yield a solutionof Compound 2B in free amine form.2.c.2. The active ester of BOC-Inp-OH (66.5 mg, 0.290 mmole) waspreformed with HOSu (33 mg, 0.290 mmole) and DIC (37 mg 0.290 mmole) inDCM (1.5 ml). After one hour diisopropylurea was removed by filtrationand the filtrate was added to the Compound 2B (free amine) solution. Theresulting solution was diluted with DCM to 4 ml and the couplingreaction was allowed to proceed for 12 hours.

The reaction mixture was then washed three times with 10% pH 5.5phosphate buffer (10 ml) and dried over Na₂SO₄. Solvent was removedunder vacuum and the concentrate was purified by flash chromatography.

2.c.3. The intermediate was deblocked using TFA (2.75 ml) and TIPS (0.5ml) in DCM (2.75 ml) for 30 minutes. Volatiles were removed from thereaction mixture under a stream of nitrogen and the residue wastriturated with ether (15 ml). After centrifugation the ether wasdecanted and the resulting solid was subjected to HPLC to yield purifiedCompound 70 in 39% yield.

Steps 2.c.1. and 2.c.2. and 2.c.3. are summarized in Scheme 2C, below.

Additional examples for synthesizing compounds according to formula IIIare provided below to further illustrate different features of thepresent invention. The examples also illustrate useful methodology forpracticing the invention. These examples do not limit the claimedinvention.

(Ac-Aib¹, Aib^(2,10), Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂ (SEQ IDNO:272)

The title peptide was synthesized on an Applied Biosystems® model 433Apeptide synthesizer (obtained from Applied Biosystems®, Foster City,Calif., U.S.A.) using Fluorenylmethyloxycarbonyl (Fmoc) chemistry. ARink Amide-4-methylbenzylhydrylamine (MBHA) resin (obtained fromNovabiochem®, San Diego, Calif.) with substitution of 0.64 mmol/g wasemployed. The Fmoc amino acids (obtained from AnaSpec®, San Jose,Calif., U.S.A.) used were Fmoc-Ala-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Aib-OH,Fmoc-Gln(Trt)-OH, Fmoc-Glu(tBu)-OH, Fmoc-His(Trt)-OH, Fmoc-Leu-OH,Fmoc-Lys(Boc)-OH, Fmoc-Phe-OH, Fmoc-Pro-OH, Fmoc-Ser(tBu)-OH andFmoc-Val-OH. In addition, Fmoc-Glu(O-2-PhiPr)—OH (obtained fromNovabiochem®, San Diego, Calif.) was used for the amino acids in 3^(rd)and 17^(th) positions. The synthesis was carried out on a 0.1 mmolscale. The Fmoc groups were removed by treating the resin with asolution of 20% piperidine in N-methylpyrrolidone (NMP) for a period ofapproximately 30 minutes. In each coupling step, the Fmoc amino acid (3eq, 0.3 mmol) was first pre-activated in 2 mL solution of 0.45M2-(1-H-benzotriazole-1-yl)-1,1,2,3-tetramethyluronium-hexafluorophosphate/1-hydroxy-benzotriazole(HBTU/HOBT) in NMP. A solution containing the activated amino acid estertogether with 1 mL of diisopropylethylamine (DIEA) and 1 mL of NMP wasintroduced to the resin. The ABI 433A® peptide synthesizer wasprogrammed to perform the following reaction cycle:

(1) washing with NMP;(2) removing Fmoc protecting group with 20% piperidine in NMP for 30minutes;(3) washing with NMP; and(4) coupling with pre-activated Fmoc amino acid for approximately 1 or 3hours.The resin was coupled successively according to the sequence of thetitle peptide. After the peptide chain was assembled, the resin waswashed completely with N,N-dimethylformamide (DMF) and dichloromethane(DCM).

At the end of the assembly of the peptide chain on the ABI 433A® peptidesynthesizer (without the Fmoc-Aib residue in A¹), the peptide-resin wastransferred to a reaction vessel on a shaker and the Fmoc was removedusing 25% piperidine in DMF for 30 minutes. The resin was then washedwith DMF. The Fmoc-Aib-OH (0.4 mmole) was coupled using TFFH(Tetramethylfluoroformamidinium Hexafluorophosphate) (obtained fromPerceptive Biosystems®, Warrington, U.K.) (0.4 mmole), HOAt (0.4 mmol),DMAP (Dimethylaminopyridine) (0.1 g) and DIEA (1.2 mmole) once for 4hours and once overnight.

The Fmoc group was removed as above and the peptide was capped usingAc₂O (acetic anhydride) (5 mmole) and DIEA (5 mmole) in DMF forapproximately 30 minutes. The PhiPr (γ-2-phenylisopropyl ester) groupswere removed from the Glutamine residues at A³ and A¹⁷ by washing with asolution of 3% TFA in DCM twice for a period of 10 minutes for eachwashing. The Boc that was partially removed from the side chain ofLysine was replaced by using Boc₂O (0.8 mmole) and DIEA (0.8 mmole) inDCM overnight. The resin was treated with PyAOP(7-Azabenzotriazol-1-yloxytris(pyrrolidino)phosphonium-hexafluorophosphate)(obtained from Applied Biosystems®, Foster City, Calif., U.S.A.) (0.6mmole), HOAt (0.6 mmole), DMAP (0.1 g) and DIEA (1.8 mmole) for 10minutes. Hexyl-NH₂(Hexylamine) (obtained from Sigma-Aldrich Chemicals®,St. Louis, Mo., U.S.A.) (2.0 mmole) was then added to the resin solutionwhich was then shaken and allowed to stand overnight.

To cleave the title peptide from the resin, the peptide-resin wastreated with a mixture of TFA, H₂O and triisopropylsilane (TIS) (9.5mL/0.85 mL/0.8 mL, respectively) for approximately 4 hours. The cleavedresin was filtered off and the remaining filtrate was poured into 200 mLof ether. A precipitate formed which was then collected bycentrifugation. The crude product was dissolved in a mixture ofacetonitrile and water which was purified on a reverse-phase preparativeHPLC system with a column (4×43 cm) of C₁₈ DYNAMAX-100 A⁰® (obtainedfrom Varian®, Walnut Creek, Calif., U.S.A.). The column was eluted overapproximately 1 hour using a linear gradient of 85% A:15% B to 60% A:40%B, where A was 0.1% TFA in water and B was 0.1% TFA in acetonitrile. Thefractions were analyzed by HPLC and those fractions found to containpure product were pooled and lyophilized to dryness. Approximately 27.1mg (6.3%) of a white solid was recovered which was assayed using HPLCand found to be approximately 97.5% pure. Electro-spray ionization massspectrometry (ESI-MS) analysis determined the molecular weight to be3477.4 which was in agreement with the calculated molecular weight of3477.19.

(Aib^(1,2,10) Glu(NH-hexyl)^(3,17))hGhrelin(1-28)-NH₂ (SEQ ID NO:212)

The titled peptide was synthesized according to the procedure describedfor Example 158, i.e., (Ac-Aib¹, Aib^(2,10),Glu(NH-Hexyl)^(3,17))hGhrelin(1-28)-NH₂) with the following exception:After coupling the last Fmoc-Aib-OH in the 1^(st) position on a shaker,the PhiPr protecting groups were removed from the Glutamine residues atA³ and A¹⁷ by washing with a 3% TFA in DCM twice for intervals lastingapproximately 10 minutes. The Boc that was partially removed from theside chain of Lysine was replaced using a solution of Boc₂O (0.8 mmole)and DIEA (0.8 mmole) in DCM. After being shaken and standing overnight,the resin was treated with a solution of PyAOP(7-Azabenzotriazol-1-yloxytris(pyrrolidino)phosphonium-hexafluorophosphate)(obtained from Applied Biosystems®, Foster City, Calif., U.S.A.) (0.6mmole), HOAt (0.6 mmole), DMAP (0.1 g) and DIEA (1.8 mmole) for 10minutes after which Hexyl-NH₂(Hexylamine) (obtained from Sigma-Aldrich,St. Louis, Mo., U.S.A.) (2.0 mmole) was then added to the solution whichwas then shaken and allowed to stand overnight. The Fmoc protectinggroup was then removed using 25% piperidine in DMF. The peptide wascleaved off from the resin and purified on a HPLC system, as detailed inthe discussion of the synthesis of Example 158 above.

Using an HPLC assay, the purity of the resulting produce was found to beapproximately 96.5%. Electro-spray ionization mass spectrometry (ESI-MS)analysis determined the molecular weight to 3435.00 which was inagreement with the calculated molecular weight of 3435.16.

B. Biological Assays

The activities of the compounds of the invention at the GHS receptor canbe and were determined using techniques such as those described in theexamples provided below. In different embodiments a ghrelin analog hasat least about 50%, at least about 60%, at least about 70%, at leastabout 80%, or at least about 90%, at least about 95%, at least about 98%or more, functional activity relative to ghrelin as determined using oneor more of the functional activity assays described below; and/or has anIC₅₀ greater than about 1,000 nM, greater than about 100 nM, or greaterthan about 50 nM, using the receptor binding assay described below. Withrespect to IC₅₀, greater refers to potency and thus indicates a lesseramount is needed to achieve binding inhibition.

Assays measuring the ability of a compound to bind a GHS receptor employa GHS receptor, a fragment of the receptor comprising a ghrelin bindingsite, a polypeptide comprising such a fragment, or a derivative of thepolypeptide. Preferably, the assay uses the GHS receptor or a fragmentthereof.

A polypeptide comprising a GHS receptor fragment that binds ghrelin canalso contain one or more polypeptide regions not found in a GHSreceptor. A derivative of such a polypeptide comprises a GHS receptorfragment that binds ghrelin along with one or more non-peptidecomponents.

The GHS receptor amino acid sequence involved in ghrelin binding can bereadily identified using labeled ghrelin or ghrelin analogs anddifferent receptor fragments. Different strategies can be employed toselect fragments to be tested to narrow down the binding region.Examples of such strategies include testing consecutive fragments ofabout 15 amino acids in length starting at the N-terminus, and testinglonger length fragments. If longer length fragments are tested, afragment binding ghrelin can be subdivided to further locate the ghrelinbinding region. Fragments used for binding studies can be generatedusing recombinant nucleic acid techniques.

Binding assays can be performed using individual compounds orpreparations containing different numbers of compounds. A preparationcontaining different numbers of compounds having the ability to bind tothe GHS receptor can be divided into smaller groups of compounds thatcan be tested to identify the compound(s) binding to the GHS receptor.In an embodiment of the present invention, a test preparation containingat least 10 compounds is used in a binding assay. Binding assays can beperformed using recombinantly produced GHS receptor polypeptides presentin different environments. Such environments include, for example, cellextracts and purified cell extracts containing the GHS receptorpolypeptide expressed from recombinant nucleic acid or naturallyoccurring nucleic acid; and also include, for example, the use of apurified GHS receptor polypeptide produced by recombinant means or fromnaturally occurring nucleic acid which is introduced into a differentenvironment.

B.1 Screening for GHS Receptor Active Compounds

Screening for GHS receptor active compounds is facilitated using arecombinantly expressed receptor. Using a recombinantly expressed GHSreceptor offers several advantages such as the ability to express thereceptor in a defined cell system so that a response to a compound atthe GHS receptor can be more readily differentiated from responses atother receptors. For example, the GHS receptor can be expressed in acell line such as HEK 293, COS 7, or CHO not normally expressing thereceptor by an expression vector, wherein the same cell line without theexpression vector can act as a control.

Screening for compounds reducing GHS receptor activity is facilitatedthrough the use of a ghrelin analog in the assay. The use of a ghrelinanalog in a screening assay provides for GHS receptor activity. Theeffect of test compounds on such activity can be measured to identify,for example, allosteric modulators and antagonists.

GHS receptor activity can be measured using different techniques such asdetecting a change in the intracellular conformation of the GHSreceptor, in the G-protein coupled activities, and/or in theintracellular messengers. Preferably, GHS receptor activity is measuredusing techniques such as those measuring intracellular Ca²⁺ Examples oftechniques well known in the art that can be employed to measure Ca²⁺include the use of dyes such as Fura-2 and the use ofCa²⁺-bioluminescent sensitive reporter proteins such as aequorin. Anexample of a cell line employing aequorin to measure G-protein activityis HEK293/aeg17 (Button, D. et al., Cell Calcium, (1993), 14(9):663-71;and Feighner, S. D. et al., Science, (1999), 284(5423):2184-8).

Chimeric receptors containing a ghrelin binding region functionallycoupled to a different G-protein can also be used to measure GHSreceptor activity. A chimeric GHS receptor contains an N-terminalextracellular domain; a transmembrane domain made up of transmembraneregions, extracellular loop regions, and intracellular loop regions; andan intracellular carboxy terminus. Techniques for producing chimericreceptors and measuring G-protein coupled responses are provided in, forexample, International Application Number WO 97/05252, and U.S. Pat. No.5,264,565, both of which are hereby incorporated by reference herein.

Ghrelin analogs can be used to stimulate GHS receptor activity. Suchstimulation can be used, for example, to study the effect of GHSreceptor modulation, to study the effect of growth hormone secretion, tolook for or study ghrelin antagonists, or to achieve a beneficial effectin a subject. It is contemplated that the ghrelin analogs of the instantinvention are useful for stimulating gastrointestinal motility.

B.1.a. Preparation of CHO-K1 Cells Expressing the Human Recombinant GHSReceptor

The cDNA for human growth hormone secretagogue receptor (hGHS-R, orghrelin receptor) was cloned by Polymerase Chain Reaction (PCR) usinghuman brain RNA as a template (Clontech, —Palo Alto, Calif.), genespecific primers flanking the full-length coding sequence of hGHS-R, (S:5′-A T G T G G A A C G C G A C G C C C A G C G A A G A G-3′ and AS:5′-TC A T G T A T T A A T A C T A G A T T C T G T C C A 3′), and Advantage 2PCR Kit (Clontech, —Palo Alto, Calif.). The PCR product was cloned intothe pCR2.1® vector using Original TA® Cloning Kit (Invitrogen, Carlsbad,Calif.). The full length human GHS-R was subcloned into the mammalianexpression vector pcDNA 3.1® (Invitrogen, Carlsbad, Calif.). The plasmidwas transfected into the Chinese hamster ovary cell line, CHO-K1(American Type Culture Collection, Rockville, Md.) by calcium phosphatemethod (Wigler, M. et al., Cell, (1977), 11(1):223-32). Single cellclones stably expressing the hGHS-R were obtained by selectingtransfected cells grown in cloning rings in RPMI 1640 media supplementedwith 10% fetal bovine serum and 1 mM sodium pyruvate containing 0.8mg/ml G418 (Gibco®, Grand Island, N.Y., U.S.A.).

B.1.b GHS-Receptor Binding Assay:

Membranes for radioligand binding studies can be and were prepared byhomogenization of the foregoing CHO-K1 cells expressing the humanrecombinant GHS receptor. The cells were homogenized in 20 ml ofice-cold 50 mM Tris-HCl using a Brinkman Polytron® (Westbury, N.Y.;setting 6, 15 sec). The homogenates were washed twice by centrifugation(39,000 g/10 min) and the final pellets were resuspended in 50 mMTris-HCl containing 2.5 mM MgCl₂ and 0.1% bovine serum albumin (BSA).For the assay, 0.4 ml aliquots were incubated with 0.05 nM (¹²⁵I)ghrelin(˜2000 Ci/mmol, Perkin Elmer Life Sciences, Boston, Mass.) with andwithout 0.05 ml of unlabeled competing test peptide. After a 60 minincubation at 4° C., the bound (¹²⁵I)ghrelin was separated from free(¹²⁵I)ghrelin by rapid filtration through GF/C filters (Brandel,Gaithersburg, Md.) which had been previously soaked in 0.5%polyethyleneimine/0.1% BSA. The filters were then washed three timeswith 5-ml aliquots of ice-cold 50 mM Tris-HCl and 0.1% BSA, and thebound radioactivity trapped on the filters was counted by gammaspectrometry (Wallac LKB, Gaithersburg, Md.). Specific binding wasdefined as the total (¹²⁵I)ghrelin bound minus that bound in thepresence of 1000 nM ghrelin (Bachem, Torrence, Calif.).

A selection of the preferred embodiments was tested using the receptorbinding assay discussed above and the results are reported in Table 1presented below.

TABLE 1 Receptor Binding Ki Values for Selected Compounds Example #COMPOUND Ki(nM) #1 H-Apc-D-1-Nal-D-Trp-2-Thi-Lys-NH₂; (SEQ ID NO: 124)0.29 #2 Inp-D-2-Nal-D-Trp-Phe-Lys-NH₂ (SEQ ID NO: 111) 0.30 #3H-Inp-D-1-Nal-D-Trp-2-Thi-Lys-NH₂ (SEQ ID NO: 112) 0.31 #4H-Apc-D-Bal-D-Trp-Phe-Lys-NH₂ (SEQ ID NO: 123) 0.32 #5H-Inp-D-Bal-D-Trp-Phe-Lys-NH₂ (SEQ ID NO: 111) 0.33 #6H-Inp-D-1-Nal-D-Trp-Phe-Apc-NH₂ (SEQ ID NO: 122) 0.36 #7H-Apc-D-Bal-D-Trp-2-Thi-Lys-NH₂ (SEQ ID NO: 128) 0.36 #8(Aib², Glu³(NH-hexyl))hGhrelin(1-28)-NH₂ (SEQ ID NO: 84) 0.38 #9H-Inp-D-Bal-D-Trp-2-Thi-Apc-NH₂ (SEQ ID NO: 151) 0.40 #10(Aib⁸)hGhrelin(1-28)-NH₂ (SEQ ID NO: 16) 0.41 #11H-Apc-D-2-Nal-D-Trp-Phe-Lys-NH₂ (SEQ ID NO: 123) 0.42 #12H-Inp-D-Bal-D-Trp-2-Thi-Lys-NH₂ (SEQ ID NO: 121) 0.42 #13H-Apc-D-1-Nal-D-Trp-Phe-Lys-NH₂ (SEQ ID NO: 131) 0.42 #14H-Apc-D-1-Nal-D-Trp-Taz-Lys-NH₂ (SEQ ID NO: 124) 0.45 #15H-Inp-D-2-Nal-D-Trp-2-Thi-Lys-NH₂ (SEQ ID NO: 113) 0.45 #16(Aib^(2,8), Glu(NH-hexyl)^(3,17))hGhrelin (1-28)-NH₂ (SEQ ID 0.45NO: 202) #17 H-Apc-D-1-Nal-D-Trp-2-Thi-Apc-NH₂ (SEQ ID NO: 137) 0.46 #18H-Apc-D-1-Nal-D-Trp-Phe-Apc-NH₂ (SEQ ID NO: 129) 0.46 #19H-Inp-D-Bal-D-Trp-Phe-Apc-NH₂ (SEQ ID NO: 122) 0.47 #20H-Apc-D-Bal-D-Trp-Taz-Lys-NH₂ (SEQ ID NO: 128) 0.50 #21(Glu³(O-hexyl))hGhrelin(1-28)-NH₂ (SEQ ID NO: 1) 0.50 #22H-Apc-D-Bal-D-Trp-2-Thi-Apc-NH₂ (SEQ ID NO: 143) 0.51 #23H-Inp-D-Bal-D-Trp-Taz-Lys-NH₂; (SEQ ID NO: 121) 0.52 #24H-Inp-D-1-Nal-D-Trp-2-Thi-Apc-NH₂ (SEQ ID NO: 147) 0.53 #25(Aib²)hGhrelin(1-28)-NH₂ (SEQ ID NO: 10) 0.57 rGhrelin 0.59 #26(2-Thi⁹)hGhrelin(1-28)-NH₂ (SEQ ID NO: 14) 0.63 #27(Aib², Taz⁹)hGhrelin(1-28)-NH₂ (SEQ ID NO: 8) 0.63 #28H-Inp-D-2-Nal-D-Trp-Phe-Apc-NH₂ (SEQ ID NO: 122) 0.64 #29(Aib², 3-Pal⁹)hGhrelin(1-28)-NH₂ (SEQ ID NO: 8) 0.65 #30H-Apc-D-Bal-D-2-Nal-Phe-Lys-NH₂ (SEQ ID NO: 132) 0.68 #31H-Apc-D-1-Nal-D-Trp-Phe-NH₂ (SEQ ID NO: 125) 0.70 #32(3-Pal⁹)hGhrelin(1-28)-NH₂ (SEQ ID NO: 14) 0.70 #33H-Apc-D-Bal-D-Trp-Phe-Apc-NH₂ (SEQ ID NO: 130) 0.71 #34H-Apc-D-1-Nal-D-Trp-2-Thi-NH₂ (SEQ ID NO: 133) 0.73 #35(Glu³(NH-Hexyl), Aib⁸)hGhrelin(1-28)-NH₂ (SEQ ID NO: 35) 0.74 #36(Aib², 4-Hyp⁷)hGhrelin(1-28)-NH₂ (SEQ ID NO: 9) 0.75 #37H-Inp-D-2-Nal-D-Trp-Taz-Lys-NH₂ (SEQ ID NO: 113) 0.80 #38H-Inp-D-Bal-D-Trp-Taz-Apc-NH₂ (SEQ ID NO: 135) 0.83 #39H-Inp-D-1-Nal-D-Trp-2-Thi-NH₂ (SEQ ID NO: 116) 0.87 #40(Asp³(O-hexyl))hGhrelin(1-28)-NH₂ (SEQ ID NO: 326) 0.88 #41H-Apc-D-Bal-D-Trp-Phe-NH₂ (SEQ ID NO: 125) 0.89 #42(Lys⁵)hGhrelin(1-28)-NH₂ (SEQ ID NO: 3) 0.89 #43(Aib², Glu³(NH-hexyl), Taz⁹)hGhrelin(1-28)-NH₂ (SEQ ID 0.90 NO: 64) #44(Aib², Dhp⁷)hGhrelin(1-28)-NH₂ (SEQ ID NO: 9) 0.91 #45H-Apc-D-2-Nal-D-Trp-2-Thi-NH₂ (SEQ ID NO: 134) 0.95 #46H-Apc-D-1-Nal-D-Trp-Taz-Apc-NH₂ (SEQ ID NO: 136) 0.98 #47H-Apc-D-Bal-D-Trp-2-Thi-NH₂ (SEQ ID NO: 144) 0.98 #48(Aib^(2,10))hGhrelin(1-28)-NH₂ (SEQ ID NO: 12) 1.02 #49(Aib^(2,8))hGhrelin(1-28)-NH₂ (SEQ ID NO: 11) 1.02 #50H-Inp-D-1-Nal-D-Trp-3-Pal-Lys-NH₂ (SEQ ID NO: 112) 1.05 #51(Aib², Glu³(NH-hexyl), 2-Thi⁹)hGhrelin(1-28)-NH₂ (SEQ ID 1.06 NO: 64)#52 (A5c²)hGhrelin(1-28)-NH₂ (SEQ ID NO: 10) 1.07 #53(Aib², Tic⁷)hGhrelin(1-28)-NH₂ (SEQ ID NO: 9) 1.08 #54(Aib², Thz⁷)hGhrelin(1-28)-NH₂ (SEQ ID NO: 9) 1.08 #55(Aib², 4-Pal⁹)hGhrelin(1-28)-NH₂ (SEQ ID NO: 8) 1.09 #56(Aib^(2,8), Glu³(NH-hexyl))hGhrelin(1-28)-NH₂ (SEQ ID NO: 27) 1.09 #57H-Inp-D-1-Nal-D-Trp-Taz-Lys-NH₂ (SEQ ID NO: 112) 1.11 #58H-Apc-D-Bal-D-Trp-Taz-Apc-NH₂ (SEQ ID NO: 136) 1.13 #59(Aib^(2,10), Glu³(NH-hexyl))hGhrelin(1-28)-NH₂ (SEQ ID NO: 28) 1.14 #60H-Inp-D-1-Nal-D-Trp-Taz-Apc-NH₂ (SEQ ID NO: 135) 1.19 #61Cys³(S(CH₂)₉CH₃)hGhrelin(1-28)-NH₂ (SEQ ID NO: 1) 1.24 #62(Aib¹)hGhrelin(1-28)-NH₂ (SEQ ID NO: 329) 1.28 #63(Ac-Gly¹, Aib²)hGhrelin(1-28)-NH₂ (SEQ ID NO: 90) 1.29 #64H-Apc-D-1-Nal-D-1-Nal-Phe-Lys-NH₂ (SEQ ID NO: 131) 1.32 #65(Aib², Pip⁷)hGhrelin(1-28)-NH₂ (SEQ ID NO: 9) 1.34 #66H-Inp-D-Bip-D-Trp-Phe-Lys-NH₂ (SEQ ID NO: 111) 1.35 #67H-Apc-D-1-Nal-D-Trp-Taz-NH₂ (SEQ ID NO: 133) 1.41 #68H-Apc-D-Bal-D-1-Nal-Phe-Lys-NH₂ (SEQ ID NO: 132) 1.46 #69H-Apc-D-Bal-D-2-Nal-Phe-Apc-NH₂ (SEQ ID NO: 130) 1.49 #70H-Inp-D-2-Nal-D-Trp-Thr(Bzl)-Lys-NH₂ (SEQ ID NO: 113) 1.55 #71H-Inp-D-2-Nal-D-Trp-3-Pal-Lys-NH₂ (SEQ ID NO: 113) 1.58 #72H-Apc-D-Bal-D-Trp-Taz-NH₂ (SEQ ID NO: 144) 1.62 #73H-Apc-D-1-Nal-D-2-Nal-Phe-Apc-NH₂ (SEQ ID NO: 129) 1.71 #74H-Apc-D-1-Nal-D-1-Nal-Phe-Apc-NH₂ (SEQ ID NO: 129) 1.99 #75(Dap³(octanesulfonyl))hGhrelin(1-28)-NH₂ (SEQ ID NO: 1) 2.00 #76(Glu³(NH-hexyl))hGhrelin(1-28)-NH₂ (SEQ ID NO: 1) 2.03 #77H-Apc-D-2-Nal-D-Trp-Taz-NH₂ (SEQ ID NO: 134) 2,11 #78H-Inp-D-Bal-D-Trp-Phe-NH₂ (SEQ ID NO: 119) 2.30 #79(Aib², Glu³(NH-hexyl), 4-Hyp⁷)hGhrelin(1-28)-NH₂ (SEQ ID 2.34 NO: 65)#80 (Aib², Glu³(NH-hexyl), 3-Pal⁹)hGhrelin(1-28)-NH₂ (SEQ ID 2.35NO: 64) #81 (Aib², Cha⁵)hGhrelin(1-28)-NH₂ (SEQ ID NO: 2) 2.98 #82(Glu³(NH-hexyl), 4-Hyp⁷)hGhrelin(1-28)-NH₂ (SEQ ID NO: 68) 3.36 #83H-Apc-D-Bal-D-1-Nal-Phe-Apc-NH₂ (SEQ ID NO: 130) 3.48 #84H-Inp-D-2-Nal-D-Trp-2-Thi-NH₂ (SEQ ID NO: 115) 4.11 #85(Aib², Glu³(NH-hexyl), 4-Pal⁹)hGhrelin(1-28)-NH₂ (SEQ ID 4.15 NO: 64)#86 (Asp³(NH-heptyl))hGhrelin(1-28)-NH₂ (SEQ ID NO: 326) 4.27 #87H-Inp-D-2-Nal-D-Trp-Thr(Bzl)-NH₂ (SEQ ID NO: 115) 4.46 #88(Aib², Abu⁶)hGhrelin(1-28)-NH₂ (SEQ ID NO: 4) 4.60 #89(Aib^(2,12), Glu³(NH-hexyl), 4-Pal⁹, Orn¹⁵)hGhrelin(1-28)-NH₂ 4.83(SEQ ID NO: 75) #90 H-Inp-D-2-Nal-D-Trp-Taz-NH₂ (SEQ ID NO: 115) 6.17#91 H-Inp-D-2-Nal-D-Trp-4-Pal-Lys-NH₂ (SEQ ID NO: 113) 7.35 #92(n-octanoyl-Gly¹)hGhrelin(1-28)-NH₂ (SEQ ID NO: 95) 10.19 #93H-Inp-D-2-Nal-D-Trp-3-Pal-NH₂ (SEQ ID NO: 115) 11.35 #94(Act²)hGhrelin(1-28)-NH₂ (SEQ ID NO: 10) 12.72 #95(n-butyryl-Gly¹)hGhrelin(1-28)-NH₂ (SEQ ID NO: 95) 12.78 #96(Aib², A6c⁵)hGhrelin(1-28)-NH₂ (SEQ ID NO: 2) 14.77 #97H-Inp-D-1-Nal-D-Trp-3-Pal-NH₂ (SEQ ID NO: 116) 16.10 #98H-Inp-D-Bip-D-Trp-Phe-NH₂ (SEQ ID NO: 117) 20.00 #99(isobutyryl-Gly¹)hGhrelin(1-28)-NH₂ (SEQ ID NO: 95) 21.85hGhrelin(1-28)-NH₂ 24.16 #100H-Inp-D-2-Nal-D-Trp-Pff-Lys-NH₂ (SEQ ID NO: 113) 25.43 #101H-Inp-D-2-Nal-D-Bal-Phe-NH₂ (SEQ ID NO: 118) 27.40 #102(A6c⁵)hGhrelin(1-28)-NH₂ (SEQ ID NO: 3) 35.82 #103H-Inp-D-2-Nal-D-Trp-Pff-NH₂ (SEQ ID NO: 115) 36.31 #104(des-Ser²)hGhrelin(1-28)-NH₂ (SEQ ID NO: 327) 39.10 #105H-Inp-D-Dip-D-Trp-Phe-Lys-NH₂ (SEQ ID NO: 111) 46.78 #106H-Inp-D-Bal-D-Trp(Ψ)-Pim (SEQ ID NO: 126) 48.73 #107H-Inp-D-1-Nal-D-Trp(Ψ)-Pim (SEQ ID NO: 126) 50.55 #108(Aib^(2,6))hGhrelin(1-28)-NH₂ (SEQ ID NO: 4) 71.55 #109H-Inp-D-Bpa-D-Trp-Phe-Lys-NH₂ (SEQ ID NO: 111) 93.75 #110H-Inp-D-2-Nal-D-Dip-Phe-NH₂ (SEQ ID NO: 118) 104.80 #111H-Inp-D-Dip-D-Trp-Phe-NH₂ (SEQ ID NO: 117) 104.83 #112H-Inp-D-2-Nal-D-Trp-4-Pal-NH₂ (SEQ ID NO: 115) 113.50 #113H-Inp-D-2-Nal-D-Trp(Ψ)-Pim (SEQ ID NO: 126) 116.68 #114Aib², Act⁶)hGhrelin(1-28)-NH₂ (SEQ ID NO: 4) 155.43 #115H-Inp-D-Trp-D-2-Nal(Ψ)-Pim (SEQ ID NO: 120) 182.00 #116H-Inp-D-2-Nal-D-Trp-Orn-Lys-NH₂ (SEQ ID NO: 113) 243.00 #117(des-Gly¹, des-Ser²)hGhrelin(1-28)-NH₂ (SEQ ID NO: 328) 283.33 #118H-Inp-D-2-Nal-D-Bpa-Phe-Lys-NH₂ (SEQ ID NO: 114) 419.00 #119H-Aib-D-Ser(Bzl)-D-Trp(Ψ)-Pim (SEQ ID NO: 127) 753.33

B.2. GHS-R Functional Activity Assays

B.2.a. In Vitro GSH Receptor Mediated Intracellular iCa²⁺ Mobilization

The foregoing CHO-K1 cells expressing the human GSH receptor wereharvested by incubation in a 0.3% EDTA/phosphate buffered salinesolution (25° C.) and washed twice by centrifugation. The washed cellswere resuspended in Hank's—buffered saline solution (HBSS) for loadingof the fluorescent Ca²⁺ indicator Fura-2AM. Cell suspensions ofapproximately 10⁶ cells/ml were incubated with 2 μM Fura-2AM for 30 minat about 25° C. Unloaded Fura-2AM was removed by centrifugation twice inHBBS, and the final suspensions were transferred to a spectrofluorometer(Hitachi F-2000) equipped with a magnetic stirring mechanism and atemperature-regulated cuvette holder. After equilibration to 37° C., theghrelin analogs were added for measurement of intracellular Ca²⁺mobilization. The excitation and emission wavelengths were 340 and 510nm, respectively.

B.2.b. In Vivo GH Release/Suppression

As is well known in the art, compounds may be tested for their abilityto stimulate or suppress release of growth hormone (GH) in vivo(Deghenghi, R. et al., Life Sciences, (1994), 54(18):1321-8; andInternational Patent Application No. PCT/EP01/07929 [WO 02/08250]). Thusfor example in order to ascertain a compound's ability to stimulate GHrelease in vivo the compound may be injected subcutaneously in 10-dayold rats at a dose of, e.g., 300 mg/kg. The circulating GH may bedetermined at, e.g., 15 minutes after injection and compared to GHlevels in rats injected with a solvent control.

B.3. Effect Upon Gastrointestinal Motility

Ghrelin has been shown to increase gastric motility and improve gastricemptying in subjects suffering from gastroparesis. Selected compounds ofthe invention can be and were tested to determine the effect of thecompounds upon gastric emptying and intestinal transit.

B.3.a. In Vivo Study of Ghrelin on Intestinal Transit

The effect of native ghrelin and a peptidyl analog of ghrelin,H-Inp-D-Bal-D-Trp-Phe-Apc-NH₂ (SEQ ID NO:122) (Example 19) on intestinaltransit was conducted. In the study, groups of eight rats were fastedfor approximately 24 hours with free access to water. Anesthetized testsubjects were administered native ghrelin, the selected analog andatropine as a control. The test subjects were administered a 2 mlcharcoal meal by esophageal gavage approximately five minutes after theinitial administration of ghrelin, the selected analog or atropine.After approximately an additional 25 minutes, the test subjects weresacrificed by cervical rupture and the small intestines were removed.The distance the charcoal traveled was measured from the pylorus. Bothghrelin and the tested peptidyl analog of ghrelin(H-Inp-D-Bal-D-Trp-Phe-Apc-NH₂) (SEQ ID NO:122) accelerated gastricintestinal transit.

B.3.b. In Vivo Study of Ghrelin on Gastric Emptying

Selected compounds of the invention can be and were tested to determinethe effect of the compounds upon gastric emptying. The effect of nativeghrelin and a peptidyl analog of ghrelin, H-Inp-D-Bal-D-Trp-Phe-Apc-NH₂(SEQ ID NO:122), on gastric emptying was conducted. In the study, groupsof eight male Sprague Dawley rats (weighing 200-250 gms) were fasted forapproximately 24 hours with free access to water. Native ghrelin, theselected ghrelin analog and a metoclopramide control compound wereadministered intravenously to anesthetized test subjects. Approximatelyfive minutes after the initial administration of native ghrelin, theselected ghrelin analog or the control compound, a 1.5 ml meal markedwith phenol red (0.5 mg/ml phenol red and 1.5% methyl cellulose in wholemilk) was administered to each test subject by esophageal gavage. Afterapproximately an additional 20 minutes, the test subjects weresacrificed by cervical rupture and the stomachs removed and individuallypulverized. The residual phenol red in the stomach of the test subjectswas extracted and was measured spectrophometrically at a wavelength of560 nm. Both ghrelin and the tested peptidyl analog of ghrelin(H-Inp-D-Bal-D-Trp-Phe-Apc-NH₂ (SEQ ID NO:122)) accelerated gastricemptying.

In other experiments, groups of eight male Sprague Dawley rats (weighing200-250 gms) were fasted for approximately 24 hours with free access towater. The animals were injected subcutaneously with either vehicle orvarying doses of native ghrelin or selected ghrelin analogs. Afterapproximately 15 minutes, 1.5 ml of a phenol red marked nutrient meal(0.5 mg/ml phenol red & 1.5% methyl cellulose in whole milk) wasadministered orally to the rats. After an additional approximately 15minutes, the subjects were sacrificed by cervical rupture and, afterclamping the pylorus & cardia, the stomach was removed. The residualphenol red in the stomach was extracted and measured byspectrophotometric methods at a wavelength of 560 nm. Both ghrelin andthe tested peptidyl analog of ghrelin (H-Inp-D-Bal-D-Trp-Phe-Apc-NH₂(SEQ ID NO:122)) accelerated gastric emptying. (see Figures)

B.3.c. Effect on POI in Rat

A 3 centimeter laparotomy was used to induce gastric ileus in maleSprague Dawley rats (weighing 200-250 gms) under isoflurane anesthesia.The abdominal muscles and skin were closed with suture and the animalswere allowed to recover for approximately two hours and forty fiveminutes. At this time, vehicle or selected ghrelin analogs wereadministered subcutaneously to the laparectomized animals. Approximately15 minutes after administration of the compounds or vehicle, the phenolred marked meal (see above) was introduced into the animals. After anadditional approximately 15 minutes, the subjects were sacrificed bycervical rupture and gastric emptying was measured as described above.Both ghrelin and the tested peptidyl analog of ghrelin(H-Inp-D-Bal-D-Trp-Phe-Apc-NH₂ (SEQ ID NO:122)) significantlyaccelerated gastric emptying under post-operative ileus conditions.

B.3.d. Effect on POI in Rat in the Presence of Morphine

A 3 centimeter laparotomy was used to induce gastric ileus in maleSprague Dawley rats (weighing 200-250 gms) under isoflurane anesthesia.The abdominal muscles and skin were closed with suture and the animalswere allowed to recover for approximately 2.5 hours at which time thelaparecotomized animals received a subcutaneous administration of 4mg/kg morphine. Approximately 15 minutes after receiving the morphine,vehicle or selected ghrelin analogs were administered subcutaneously tothe laparectomized animals. Approximately 15 minutes afteradministration of the compounds or vehicle, the phenol red marked meal(see above) was introduced into the animals. After an additionalapproximately 15 minutes, the subjects were sacrificed by cervicalrupture and gastric emptying was measured as described above. As can beseen in the Figures, ghrelin and its analog significantly accelerategastric emptying in the presence of morphine and post-operative ileusconditions.

One skilled in the art would know that assays similar to those describedherein may be used to determine the effect of a ghrelin analog upongastric emptying and intestinal transit.

Administration

Ghrelin analogs can be formulated and administered to a subject usingthe guidance provided herein along with techniques well known in theart. The preferred route of administration ensures that an effectiveamount of compound reaches the target. Guidelines for pharmaceuticaladministration in general are provided in, for example, Remington'sPharmaceutical Sciences 18th Edition, Ed. Gennaro, Mack Publishing,1990, and Modern Pharmaceutics 2^(nd) Edition, Eds. Banker and Rhodes,Marcel Dekker, Inc., 1990, both of which are hereby incorporated byreference herein. Ghrelin analogs can be prepared as acidic or basicsalts. Pharmaceutically acceptable salts (in the form of water- oroil-soluble or dispersible products) include conventional non-toxicsalts or the quaternary ammonium salts that are formed, e.g., frominorganic or organic acids or bases. Examples of such salts include acidaddition salts such as acetate, adipate, alginate, aspartate, benzoate,benzenesulfonate, bisulfate, butyrate, citrate, camphorate,camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate,ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate,hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide,hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate,methanesulfonate, 2-naphthalenesulfonate, nicotinate, oxalate, pamoate,pectinate, persulfate, 3-phenylpropionate, picrate, pivalate,propionate, succinate, tartrate, thiocyanate, tosylate, and undecanoate;and base salts such as ammonium salts, alkali metal salts such as sodiumand potassium salts, alkaline earth metal salts such as calcium andmagnesium salts, salts with organic bases such as dicyclohexylaminesalts, N-methyl-D-glucamine, and salts with amino acids such as arginineand lysine.

Ghrelin analogs can be administered using different routes includingoral, nasal, by injection, transdermal, and transmucosally. Activeingredients to be administered orally as a suspension can be preparedaccording to techniques well known in the art of pharmaceuticalformulation and may contain microcrystalline cellulose for impartingbulk, alginic acid or sodium alginate as a suspending agent,methylcellulose as a viscosity enhancer, and sweeteners/flavoringagents. As immediate release tablets, these compositions may containmicrocrystalline cellulose, dicalcium phosphate, starch, magnesiumstearate and lactose and/or other excipients, binders, extenders,disintegrants, diluents and lubricants.

Administered by nasal aerosol or inhalation formulations may beprepared, for example, as solutions in saline, employing benzyl alcoholor other suitable preservatives, absorption promoters to enhancebioavailability, employing fluorocarbons, and/or employing othersolubilizing or dispersing agents.

Ghrelin analogs may also be administered in intravenous (both bolus andinfusion), intraperitoneal, subcutaneous, topical with or withoutocclusion, or intramuscular form. When administered by injection, theinjectable solution or suspension may be formulated using suitablenon-toxic, parenterally-acceptable diluents or solvents, such asRinger's solution or isotonic sodium chloride solution, or suitabledispersing or wetting and suspending agents, such as sterile, bland,fixed oils, including synthetic mono- or diglycerides, and fatty acids,including oleic acid.

Suitable dosing regimens are preferably determined taking into accountfactors well known in the art including type of subject being dosed;age, weight, sex and medical condition of the subject; the route ofadministration; the renal and hepatic function of the subject; thedesired effect; and the particular compound employed.

Optimal precision in achieving concentrations of drug within the rangethat yields efficacy without toxicity requires a regimen based on thekinetics of the drug's availability to target sites. This involves aconsideration of the distribution, equilibrium, and elimination of adrug. The daily dose for a subject is expected to be between 0.01 and1,000 mg per subject per day.

Ghrelin analogs can be provided in a kit. Such a kit typically containsan active compound in dosage forms for administration. A dosage formcontains a sufficient amount of active compound such that a desirableeffect can be obtained when administered to a subject during regularintervals, such as 1 to 6 times a day, during the course of 1 or moredays. Preferably, a kit contains instructions indicating the use of thedosage form to achieve a desirable affect and the amount of dosage formto be taken over a specified time period.

The invention has been described in an illustrative manner, and it is tobe understood that the terminology which has been used is intended to bein the nature of words of description rather than of limitation.Obviously, many modifications and variations of the present inventionare possible in light of the above teachings. It is, therefore, to beunderstood that within the scope of the appended claims the inventionmay be practiced otherwise than as specifically described.

The patent and scientific literature referred to herein representsknowledge that is available to those with skill in the art. All patents,patent publications and other publications cited herein are herebyincorporated by reference in their entirety.

OTHER EMBODIMENTS

The foregoing description has been limited to specific embodiments ofthis invention. It will be apparent however, that variations andmodifications may be made to the invention, with the attainment of someor all of the advantages of the invention. Such embodiments are alsowithin the scope of the following claims.

1. A method of stimulating the motility of the gastrointestinal systemin a patient, said method comprising administering a peptidyl analog ofghrelin, a prodrug thereof, or a pharmaceutically acceptable salt ofsaid analog or said prodrug.
 2. The method of claim 1, wherein saidpatient is experiencing postoperative ileus following gastrointestinalsurgery.
 3. (canceled)
 4. The method of claim 3 wherein said peptidylanalog of ghrelin comprises the following formula (I):(R²R³)-A¹-A²-A³-A⁴-A⁵-A⁶-A⁷-A⁸-A⁹-A¹⁰-A¹¹-A¹²-A¹³-A¹⁴-A¹⁵-A¹⁶-A¹⁷-A¹⁸-A¹⁹-A²⁰-A²¹-A²²-A²³-A²⁴-A²⁵-A²⁶-A²⁷-A²⁸-R¹  (I)wherein: A¹ is Gly, Aib, Ala, B-Ala, or Acc; A² is Ser, Aib, Act, Ala,Acc, Abu, Ava, Thr, or Val; A³ is Ser, Ser(C(O)—R⁴), Asp(O—R⁸),Asp(NH—R⁹), Cys(S—R¹⁴), Dap(S(O)₂—R¹⁰) Dab(S(O)₂—R¹¹), Glu(O—R⁶),Glu(NH—R⁷), Thr, Thr(C(O)—R⁵), or HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O); A⁴ isPhe, Acc, Aic, Cha, 2-Fua, 1-Nal, 2-Nal, 2-Pal, 3-Pal, 4-Pal, hPhe,(X¹,X²,X³,X⁴,X⁵)Phe, Taz, 2-Thi, 3-Thi, Trp, or Tyr; A⁵ is Leu, Abu,Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle, or Val; A⁶ is Ser,Abu, Acc, Act, Aib, Ala, Gly, Thr, or Val; A⁷ is Pro, Dhp, Dmt, 3-Hyp,4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, or deleted; A⁸ is Glu, Acc, Aib,Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O),or deleted; A⁹ is His, Apc, Aib, Acc, 2-Fua, 2-Pal, 3-Pal, 4-Pal, Taz,2-Thi, 3-Thi, (X¹,X²,X³,X⁴,X⁵-)Phe or deleted; A¹⁰ is Gln, Acc, Aib,Asn, Asp, Glu, or deleted; A¹¹ is Arg, Apc, hArg, Dab, Dap, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; A¹² is Val, Abu, Acc, Aib,Ala, Cha, Nva, Gly, Ile, Leu, Nle, Tle, or deleted; A¹³ is Gln, Acc,Aib, Asn, Asp, Glu, or deleted; A¹⁴ is Gln, Acc, Aib, Asn, Asp, Glu, ordeleted; A¹⁵ is Arg, hArg, Acc, Aib, Apc, Dab, Dap, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; A¹⁶ is Lys, Acc, Aib, Apc,Arg, hArg, Dab, Dap, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted;A¹⁷ is Glu, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; A¹⁸ is Ser, Abu, Acc, Act,Aib, Ala, Thr, Val, or deleted; A¹⁹ is Lys, Acc, Aib, Apc, Arg, hArg,Dab, Dap, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; A²⁰ is Lys,Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; A²¹ is Pro, Dhp, Dmt,3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, or deleted; A²² is Pro, Dhp,Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, or deleted; A²³ is Abu,Acc, Act, Aib, Ala, Apc, Gly, Nva, Val, or deleted; A²⁴ is Lys, Acc,Aib, Apc, Arg, hArg, Dab, Dap, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), ordeleted; A²⁵ is Leu, Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe,Tle, Val, or deleted; A²⁶ is Gln, Aib, Asn, Asp, Glu, or deleted; A²⁷ isPro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, or deleted;A²⁸ is Acc, Aib, Apc, Arg, hArg, Dab, Dap, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; R₁ is —OH, —NH₂,—(C₁-C₃₀)alkoxy, or NH—X⁶—CH₂—Z⁰, wherein X⁶ is a (C₁-C₁₂)alkyl,(C₂-C₁₂)alkenyl, and Z⁰ is —H, —OH, —CO₂H or —C(O)—NH₂; R² and R³ eachis, independently for each occurrence, H, (C₁-C₂₀)alkyl or (C₁-C₂₀)acyl;R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹ and R¹⁴ each is, independently for eachoccurrence, (C₁-C₄₀)alkyl, (C₂-C₄₀)alkenyl, substituted (C₁-C₄₀) alkyl,substituted (C₂-C₄₀) alkenyl, alkylaryl, substituted alklyaryl, aryl orsubstituted aryl; R¹² and R¹³ each is, independently for eachoccurrence, H, (C₁-C₄₀)alkyl, (C₁-C₄₀)acyl, (C₁-C₃₀)alkylsulfonyl, or—C(NH)—NH₂, wherein when R¹² is (C₁-C₄₀)acyl, (C₁-C₃₀)alkylsulfonyl, or—C(NH)—NH₂, then R¹³ is H or (C₁-C₄₀)alkyl; n is, independently for eachoccurrence, 1, 2, 3, 4 or 5; X¹, X², X³, X⁴, and X⁵ each is,independently for each occurrence, H, F, Cl, Br, I, (C₁₋₁₀)alkyl,substituted (C₁₋₁₀)alkyl, aryl, substituted aryl, OH, NH₂, NO₂, or CN;provided that the peptide contains at least one amino acid selected fromthe groups consisting of: A² is Aib, Acc, or Act; A³ is Dap(S(O)₂—R¹⁰),Dab(S(O)₂—R¹¹), Glu(NH-Hexyl), or Cys(S-Decyl); A⁵ is Abu, Acc, Aib,Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle, or Val; A⁶ is Abu, Acc, Act,Aib, Ala, Gly, Thr or Val; A⁷ is Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic,Pip, Thz or Tic; A⁸ is Acc, Aib, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn,or HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O); A⁹ is Aib, Acc, Apc, 2-Fua, 2-Pal,3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi, or (X¹,X²,X³,X⁴,X⁵-)Phe; and A¹⁰ isAcc, Aib, Asn, Asp, or Glu; and further provided that the peptide is not(Lys⁸)hGhrelin(1-8)-NH₂ or (Arg⁸)hGhrelin(1-8)-NH₂; or apharmaceutically acceptable salt thereof.
 5. The method of claim 3wherein said peptidyl ghrelin analog comprises the following formula(II):R¹-A¹-A²-A³-A⁴-A⁵-R²   (II) wherein: A¹ is Aib, Apc or Inp; A² is D-Bal,D-Bip, D-Bpa, D-Dip, D-1-Nal, D-2-Nal, D-Ser(Bzl), or D-Trp; A³ isD-Bal, D-Bip, D-Bpa, D-Dip, D-1-Nal, D-2-Nal, D-Ser(Bzl), or D-Trp; A⁴is 2-Fua, Orn, 2-Pal, 3-Pal, 4-Pal, Pff, Phe, Pim, Taz, 2-Thi, 3-Thi,Thr(Bzl); A⁵ is Apc, Dab, Dap, Lys, Orn, or deleted; R¹ is hydrogen,(C₁₋₆)alkyl, (C₅₋₁₄)aryl, (C₁₋₆)alkyl(C₅₋₁₄)aryl, (C₃₋₈)cycloakyl, or(C₂₋₁₀)acyl; and R² is OH or NH₂; provided that when A⁵ is Dab, Dap,Lys, or Orn, then: A² is D-Bip, D-Bpa, D-Dip or D-Bal; or A³ is D-Bip,D-Bpa, D-Dip or D-Bal; or A⁴ is 2-Thi, 3-Thi, Taz, 2-Fua, 2-Pal, 3-Pal,4-Pal, Orn, Thr(Bzl), or Pff; when A⁵ is deleted, then: A³ is D-Bip,D-Bpa, or D-Dip; or A⁴ is 2-Fua, Pff, Taz, or Thr(Bzl); or A¹ is Apcwhen A² is D-Bip, D-Bpa, D-Dip or D-Bal; or A³ is D-Bip, D-Bpa, D-Dip orD-Bal; or A⁴ is 2-Thi, 3-Thi, Orn, 2-Pal, 3-Pal or 4-Pal; or apharmaceutically acceptable salt thereof.
 6. A method of claim 3 whereinsaid peptidyl ghrelin analog comprises the following formula (III):(R²R³)-A¹-A²-A³-A⁴-A⁵-A⁶-A⁷-A⁸-A⁹-A¹⁰-A¹¹-A¹²-A¹³-A¹⁴-A¹⁵-A¹⁶-A¹⁷-A¹⁸-A¹⁹-A²⁰-A²¹-A²²-A²³-A²⁴-A²⁵-A²⁶-A²⁷-A²⁸-R¹  (III) wherein: A¹ is Gly, Aib, Ala, B-Ala, Acc or Gly(myristyl); A² isSer, Aib, Ala, Acc, Abu, Act, Ava, Thr or Val; A³ is Ser, Ser(C(O)—R⁴),Asp(O—R⁸), Asp(NH—R⁹), Cys(S—R¹⁴), Dap(S(O)₂—R¹⁰) Dab(S(O)₂—R¹¹),Glu(O—R⁶), Glu(NH—R⁷), Thr(C(O)—R⁵) or HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O);A⁴ is Phe, Acc, Aic, Cha, 2-Fua, 1-Nal, 2-Nal, 2-Pal, 3-Pal, 4-Pal,hPhe, (X¹,X²,X³,X⁴,X⁵)Phe, Taz, 2-Thi, 3-Thi, Trp or Tyr; A⁵ is Leu,Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle or Val; A⁶ isSer, Abu, Acc, Act, Aib, Ala, Gly, Thr or Val; A⁷ is Pro, Dhp, Dmt,3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz or Tic; A⁸ is Glu, Acc, Aib, Arg,Asn, Asp, Dab, Dap, Gln, Lys, Orn or HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O); A⁹is His, Apc, Aib, Acc, 2-Fua, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi or(X¹, X², X³, X⁴, and X⁵-)Phe; A¹⁰ is Gln, Acc, Aib, Asn, Asp or Glu; A¹¹is Arg, Apc, hArg, Dab, Dap, Lys, Orn orHN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O); A¹² is Val, Abu, Acc, Aib, Ala, Cha,Nva, Gly, Ile, Leu, Nle, Tle or Cha; A¹³ is Gln, Acc, Aib, Asn, Asp orGlu; A¹⁴ is Gln, Acc, Aib, Asn, Asp or Glu; A¹⁵ is Arg, hArg, Acc, Aib,Apc, Dab, Dap, Lys, Orn, Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶),Glu(NH—R⁷), Asp(O—R⁸), Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹) HNCH((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R₁₄), Cys(R¹⁵), hCys(S—R¹⁶) orhCys(R¹⁷); A¹⁶ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn,Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸),Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹),HNCH((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶),hCys(R¹⁷) or deleted; A¹⁷ is Glu, Arg, Asn, Asp, Dab, Dap, Gln, Lys,Orn, Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸),Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹) HNCH((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶),hCys(R¹⁷), Lys(biotinyl) or deleted; A¹⁸ is Ser, Abu, Acc, Act, Aib,Ala, Thr, Val, Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷),Asp(O—R⁸), Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹),HNCH—((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶),hCys(R¹⁷), or deleted; A¹⁹ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap,Orn, Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸),Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹),HNCH—((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶),hCys(R¹⁷), or deleted; A²⁰ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap,Orn, Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O-R⁶), Glu(NH—R⁷), Asp(O—R⁸),Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹),HNCH—((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶),hCys(R¹⁷), or deleted; A²¹ is Pro, Dhp, Dmt, Inc, 3-Hyp, 4-Hyp, Ktp,Oic, Pip, Thz, Tic or deleted; A²² is Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc,Ktp, Oic, Pip, Thz, Tic or deleted; A²³ is Abu, Acc, Act, Aib, Ala, Apc,Gly, Nva, Val or deleted; A²⁴ is Lys, Acc, Aib, Apc, Arg, hArg, Dab,Dap, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O) or deleted; A²⁵ is Leu, Abu,Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle, Val or deleted; A²⁶is Gln, Aib, Asn, Asp, Glu or deleted; A²⁷ is Pro, Dhp, Dmt, 3-Hyp,4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic or deleted; A²⁸ is Acc, Aib, Apc,Arg, hArg, Dab, Dap, Lys, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O) ordeleted; R¹ is —OH, —NH₂, —(C₁-C₃₀)alkoxy or NH—X⁶—CH₂—Z⁰, wherein X⁶ isa (C₁-C₁₂)alkyl, (C₂-C₁₂)alkenyl and Z⁰ is —H, —OH, —CO₂H or —C(O)—NH₂;R² and R³ is, independently for each occurrence thereof, selected fromthe group consisting of H, (C₁-C₃₀)alkyl, (C₁-C₃₀)heteroalkyl,(C₁-C₃₀)acyl, (C₂-C₃₀)alkenyl, (C₂-C₃₀)alkynyl, aryl(C₁-C₃₀)alkyl,aryl(C₁-C₃₀)acyl, substituted (C₁-C₃₀)alkyl, substituted(C₁-C₃₀)heteroalkyl, substituted (C₂-C₃₀)acyl, substituted(C₂-C₃₀)alkenyl, substituted aryl(C₁-C₃₀)alkyl and substitutedaryl(C₁-C₃₀)acyl; R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is, independently for each occurrence thereof, selected from thegroup consisting of (C₁-C₄₀)alkyl, (C₂-C₄₀)alkenyl, substituted (C₁-C₄₀)alkyl, substituted (C₂-C₄₀) alkenyl, alkylaryl, substituted alklyaryl,aryl and substituted aryl; R¹² and R¹³ is, independently for eachoccurrence thereof, selected from the group consisting of H,(C₁-C₄₀)alkyl, (C₁-C₄₀)acyl, (C₁-C₃₀)alkylsulfonyl, biotinyl and—C(NH)—NH₂, X¹, X², X³, X⁴, and X⁵ is, independently for each occurrencethereof, selected from the group consisting of H, F, Cl, Br, I,(C₁₋₁₀)alkyl, substituted (C₁₋₁₀)alkyl, aryl, substituted aryl, OH, NH₂,NO₂ and CN; and n is, independently for each occurrence thereof, 1, 2,3, 4 or 5; provided that: (I). when R² is (C₁-C₃₀)acyl,aryl(C₁-C₃₀)acyl, substituted (C₂-C₃₀)acyl, or substitutedaryl(C₁-C₃₀)acyl, R³ is H, (C₁-C₃₀)alkyl, (C₁-C₃₀)heteroalkyl,(C₂-C₃₀)alkenyl, aryl(C₁-C₃₀)alkyl, substituted (C₁-C₃₀)alkyl,substituted (C₁-C₃₀)heteroalkyl, substituted (C₂-C₃₀)alkenyl orsubstituted aryl(C₁-C₃₀)alkyl; (II). when R¹² is (C₁-C₄₀)acyl,(C₁-C₃₀)alkylsulfonyl, biotinyl or —C(NH)—NH₂, then R¹³ is H or(C₁-C₄₀)alkyl; (III). at least one of A¹⁵, A¹⁶, A¹⁷, A¹⁸, A¹⁹ or A²⁰must be selected from the group consisting of Ser(C(O)—R⁴),Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸), Asp(NH₂5 R⁹),Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹), HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O),Cys(S—R¹⁴) Cys(R¹⁵), hCys(S—R¹⁶) and hCys(R¹⁷); and (IV). when any ofthe group consisting of A¹⁵, A¹⁶, A¹⁷, A¹⁹ and A²⁰ isHNCH((CH₂)_(n)—N(R¹²R¹³))—C(O), then R¹² must be biotinylated; or apharmaceutically acceptable salt thereof. 7-10. (canceled)
 11. A methodof treating opioid-related bowel dysfunction in a patent, said methodcomprising administering a peptidyl analog of ghrelin, a prodrugthereof, or a pharmaceutically acceptable salt of said analog or saidprodrug.
 12. The method of claim 11, wherein said peptidyl analog ofghrelin comprises the following formula (I):(R²R³)-A¹-A²-A³-A⁴-A⁵-A⁶-A⁷-A⁸-A⁹-A¹⁰-A¹¹-A¹²-A¹³-A¹⁴-A¹⁵-A¹⁶-A¹⁷-A¹⁸-A¹⁹-A²⁰-A²¹-A²²-A²³-A²⁴-A²⁵-A²⁶-A²⁷-A²⁸-R¹  (I)wherein: A¹ is Gly, Aib, Ala, B-Ala, or Acc; A² is Ser, Aib, Act, Ala,Acc, Abu, Ava, Thr, or Val; A³ is Ser, Ser(C(O)—R⁴), Asp(O—R⁸),Asp(NH—R⁹), Cys(S—R¹⁴), Dap(S(O)₂—R¹⁰) Dab(S(O)₂—R¹¹), Glu(O—R⁶),Glu(NH—R⁷), Thr, Thr(C(O)—R⁵), or HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O); A⁴ isPhe, Acc, Aic, Cha, 2-Fua, 1-Nal, 2-Nal, 2-Pal, 3-Pal, 4-Pal, hPhe,(X¹,X²,X³,X⁴,X⁵)Phe, Taz, 2-Thi, 3-Thi, Trp, or Tyr; A⁵ is Leu, Abu,Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle, or Val; A⁶ is Ser,Abu, Acc, Act, Aib, Ala, Gly, Thr, or Val; A⁷ is Pro, Dhp, Dmt, 3-Hyp,4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, or deleted; A⁸ is Glu, Acc, Aib,Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O),or deleted; A⁹ is His, Apc, Aib, Acc, 2-Fua, 2-Pal, 3-Pal, 4-Pal, Taz,2-Thi, 3-Thi, (X¹,X²,X³,X⁴,X⁵-)Phe or deleted; A¹⁰ is Gln, Acc, Aib,Asn, Asp, Glu, or deleted; A¹¹ is Arg, Apc, hArg, Dab, Dap, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; A¹² is Val, Abu, Acc, Aib,Ala, Cha, Nva, Gly, Ile, Leu, Nle, Tle, or deleted; A¹³ is Gln, Acc,Aib, Asn, Asp, Glu, or deleted; A¹⁴ is Gln, Acc, Aib, Asn, Asp, Glu, ordeleted; A¹⁵ is Arg, hArg, Acc, Aib, Apc, Dab, Dap, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; A¹⁶ is Lys, Acc, Aib, Apc,Arg, hArg, Dab, Dap, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted;A¹⁷ is Glu, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; A¹⁸ is Ser, Abu, Acc, Act,Aib, Ala, Thr, Val, or deleted; A¹⁹ is Lys, Acc, Aib, Apc, Arg, hArg,Dab, Dap, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; A²⁰ is Lys,Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; A²¹ is Pro, Dhp, Dmt,3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, or deleted; A²² is Pro, Dhp,Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, or deleted; A²³ is Abu,Acc, Act, Aib, Ala, Apc, Gly, Nva, Val, or deleted; A²⁴ is Lys, Acc,Aib, Apc, Arg, hArg, Dab, Dap, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), ordeleted; A²⁵ is Leu, Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe,Tle, Val, or deleted; A²⁶ is Gln, Aib, Asn, Asp, Glu, or deleted; A²⁷ isPro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic, or deleted;A²⁸ is Acc, Aib, Apc, Arg, hArg, Dab, Dap, Lys, Orn,HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O), or deleted; R₁ is —OH, —NH₂,—(C₁-C₃₀)alkoxy, or NH—X⁶—CH₂—Z⁰, wherein X⁶ is a (C₁-C₁₂)alkyl,(C₂-C₁₂)alkenyl, and Z⁰ is —H, —OH, —CO₂H or —C(O)—NH₂; R² and R³ eachis, independently for each occurrence, H, (C₁-C₂₀)alkyl or (C₁-C₂₀)acyl;R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹ and R¹⁴ each is, independently for eachoccurrence, (C₁-C₄₀)alkyl, (C₂-C₄₀)alkenyl, substituted (C₁-C₄₀) alkyl,substituted (C₂-C₄₀) alkenyl, alkylaryl, substituted alklyaryl, aryl orsubstituted aryl; R¹² and R¹³ each is, independently for eachoccurrence, H, (C₁-C₄₀)alkyl, (C₁-C₄₀)acyl, (C₁-C₃₀)alkylsulfonyl, or—C(NH)—NH₂, wherein when R¹² is (C₁-C₄₀)acyl, (C₁-C₃₀)alkylsulfonyl, or—C(NH)—NH₂, then R¹³ is H or (C₁-C₄₀)alkyl; n is, independently for eachoccurrence, 1, 2, 3, 4 or 5; X¹, X², X³, X⁴, and X⁵ each is,independently for each occurrence, H, F, Cl, Br, I, (C₁₋₁₀)alkyl,substituted (C₁₋₁₀)alkyl, aryl, substituted aryl, OH, NH₂, NO₂, or CN;provided that the peptide contains at least one amino acid selected fromthe groups consisting of: A² is Aib, Acc, or Act; A³ is Dap(S(O)₂—R¹⁰),Dab(S(O)₂—R¹¹), Glu(NH-Hexyl), or Cys(S-Decyl); A⁵ is Abu, Acc, Aib,Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle, or Val; A⁶ is Abu, Acc, Act,Aib, Ala, Gly, Thr or Val; A⁷ is Dhp, Dmt, 3-Hyp, 4-Hyp, Inc, Ktp, Oic,Pip, Thz or Tic; A⁸ is Acc, Aib, Arg, Asn, Asp, Dab, Dap, Gln, Lys, Orn,or HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O); A⁹ is Aib, Acc, Apc, 2-Fua, 2-Pal,3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi, or (X¹,X²,X³,X⁴,X⁵-)Phe; and A¹⁰ isAcc, Aib, Asn, Asp, or Glu; and further provided that the peptide is not(Lys⁸)hGhrelin(1-8)-NH₂ or (Arg⁸)hGhrelin(1-8)-NH₂; or apharmaceutically acceptable salt thereof.
 13. The method of claim 11wherein said peptidyl ghrelin analog comprises the following formula(II):R¹-A¹-A²-A³-A⁴-A⁵-R²   (II) wherein: A¹ is Aib, Apc or Inp; A² is D-Bal,D-Bip, D-Bpa, D-Dip, D-1-Nal, D-2-Nal, D-Ser(Bzl), or D-Trp; A³ isD-Bal, D-Bip, D-Bpa, D-Dip, D-1-Nal, D-2-Nal, D-Ser(Bzl), or D-Trp; A⁴is 2-Fua, Orn, 2-Pal, 3-Pal, 4-Pal, Pff, Phe, Pim, Taz, 2-Thi, 3-Thi,Thr(Bzl); A⁵ is Apc, Dab, Dap, Lys, Orn, or deleted; R¹ is hydrogen,(C₁₋₆)alkyl, (C₅₋₁₄)aryl, (C₁₋₆)alkyl(C₅₋₁₄)aryl, (C₃₋₈)cycloakyl, or(C₂₋₁₀)acyl; and R² is OH or NH₂; provided that when A⁵ is Dab, Dap,Lys, or Orn, then: A² is D-Bip, D-Bpa, D-Dip or D-Bal; or A³ is D-Bip,D-Bpa, D-Dip or D-Bal; or A⁴ is 2-Thi, 3-Thi, Taz, 2-Fua, 2-Pal, 3-Pal,4-Pal, Orn, Thr(Bzl), or Pff; when A⁵ is deleted, then: A³ is D-Bip,D-Bpa, or D-Dip; or A⁴ is 2-Fua, Pff, Taz, or Thr(Bzl); or A¹ is Apcwhen A² is D-Bip, D-Bpa, D-Dip or D-Bal; or A³ is D-Bip, D-Bpa, D-Dip orD-Bal; or A⁴ is 2-Thi, 3-Thi, Orn, 2-Pal, 3-Pal or 4-Pal; or apharmaceutically acceptable salt thereof.
 14. A method of claim 11wherein said peptidyl ghrelin analog comprises the following formula(III): formula (III):(R²R³)-A¹-A²-A³-A⁴-A⁵-A⁶-A⁷-A⁸-A⁹-A¹⁰-A¹¹-A¹²-A¹³-A¹⁴-A¹⁵-A¹⁶-A¹⁷-A¹⁸-A¹⁹-A²⁰-A²¹-A²²-A²³-A²⁴-A²⁵-A²⁶-A²⁷-A²⁸-R¹  (III) wherein: A¹ is Gly, Aib, Ala, B-Ala, Acc or Gly(myristyl); A² isSer, Aib, Ala, Acc, Abu, Act, Ava, Thr or Val; A³ is Ser, Ser(C(O)—R⁴),Asp(O—R⁸), Asp(NH—R⁹), Cys(S—R¹⁴), Dap(S(O)₂—R¹⁰) Dab(S(O)₂—R¹¹),Glu(O—R⁶), Glu(NH—R⁷), Thr(C(O)—R⁵) or HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O);A⁴ is Phe, Acc, Aic, Cha, 2-Fua, 1-Nal, 2-Nal, 2-Pal, 3-Pal, 4-Pal,hPhe, (X¹,X²,X³,X⁴,X⁵)Phe, Taz, 2-Thi, 3-Thi, Trp or Tyr; A⁵ is Leu,Abu, Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle or Val; A⁶ isSer, Abu, Acc, Act, Aib, Ala, Gly, Thr or Val; A⁷ is Pro, Dhp, Dmt,3-Hyp, 4-Hyp, Inc, Ktp, Oic, Pip, Thz or Tic; A⁸ is Glu, Acc, Aib, Arg,Asn, Asp, Dab, Dap, Gln, Lys, Orn or HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O); A⁹is His, Apc, Aib, Acc, 2-Fua, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi or(X¹, X², X³, X⁴, and X⁵-)Phe; A¹⁰ is Gln, Acc, Aib, Asn, Asp or Glu; A¹¹is Arg, Apc, hArg, Dab, Dap, Lys, Orn orHN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O); A¹² is Val, Abu, Acc, Aib, Ala, Cha,Nva, Gly, Ile, Leu, Nle, Tle or Cha; A¹³ is Gln, Acc, Aib, Asn, Asp orGlu; A¹⁴ is Gln, Acc, Aib, Asn, Asp or Glu; A¹⁵ is Arg, hArg, Acc, Aib,Apc, Dab, Dap, Lys, Orn, Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶),Glu(NH—R⁷), Asp(O—R⁸), Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹) HNCH((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R₁₄), Cys(R¹⁵), hCys(S—R¹⁶) orhCys(R¹⁷); A¹⁶ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap, Orn,Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸),Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹),HNCH((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶),hCys(R¹⁷) or deleted; A¹⁷ is Glu, Arg, Asn, Asp, Dab, Dap, Gln, Lys,Orn, Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸),Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹) HNCH((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶),hCys(R¹⁷), Lys(biotinyl) or deleted; A¹⁸ is Ser, Abu, Acc, Act, Aib,Ala, Thr, Val, Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷),Asp(O—R⁸), Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹),HNCH—((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶),hCys(R¹⁷), or deleted; A¹⁹ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap,Orn, Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸),Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹),HNCH—((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶),hCys(R¹⁷), or deleted; A²⁰ is Lys, Acc, Aib, Apc, Arg, hArg, Dab, Dap,Orn, Ser(C(O)—R⁴), Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸),Asp(NH—R⁹), Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹),HNCH—((CH₂)_(n)—N(R¹²R¹³))—C(O), Cys(S—R¹⁴), Cys(R¹⁵), hCys(S—R¹⁶),hCys(R¹⁷), or deleted; A²¹ is Pro, Dhp, Dmt, Inc, 3-Hyp, 4-Hyp, Ktp,Oic, Pip, Thz, Tic or deleted; A²² is Pro, Dhp, Dmt, 3-Hyp, 4-Hyp, Inc,Ktp, Oic, Pip, Thz, Tic or deleted; A²³ is Abu, Acc, Act, Aib, Ala, Apc,Gly, Nva, Val or deleted; A²⁴ is Lys, Acc, Aib, Apc, Arg, hArg, Dab,Dap, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O) or deleted; A²⁵ is Leu, Abu,Acc, Aib, Ala, Cha, Ile, hLeu, Nle, Nva, Phe, Tle, Val or deleted; A²⁶is Gln, Aib, Asn, Asp, Glu or deleted; A²⁷ is Pro, Dhp, Dmt, 3-Hyp,4-Hyp, Inc, Ktp, Oic, Pip, Thz, Tic or deleted; A²⁸ is Acc, Aib, Apc,Arg, hArg, Dab, Dap, Lys, Orn, HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O) ordeleted; R¹ is —OH, —NH₂, —(C₁-C₃₀)alkoxy or NH—X⁶—CH₂—Z⁰, wherein X⁶ isa (C₁-C₁₂)alkyl, (C₂-C₁₂)alkenyl and Z⁰ is —H, —OH, —CO₂H or —C(O)—NH₂;R² and R³ is, independently for each occurrence thereof, selected fromthe group consisting of H, (C₁-C₃₀)alkyl, (C₁-C₃₀)heteroalkyl,(C₁-C₃₀)acyl, (C₂-C₃₀)alkenyl, (C₂-C₃₀)alkynyl, aryl(C₁-C₃₀)alkyl,aryl(C₁-C₃₀)acyl, substituted (C₁-C₃₀)alkyl, substituted(C₁-C₃₀)heteroalkyl, substituted (C₂-C₃₀)acyl, substituted(C₂-C₃₀)alkenyl, substituted aryl(C₁-C₃₀)alkyl and substitutedaryl(C₁-C₃₀)acyl; R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is, independently for each occurrence thereof, selected from thegroup consisting of (C₁-C₄₀)alkyl, (C₂-C₄₀)alkenyl, substituted (C₁-C₄₀)alkyl, substituted (C₂-C₄₀) alkenyl, alkylaryl, substituted alklyaryl,aryl and substituted aryl; R¹² and R¹³ is, independently for eachoccurrence thereof, selected from the group consisting of H,(C₁-C₄₀)alkyl, (C₁-C₄₀)acyl, (C₁-C₃₀)alkylsulfonyl, biotinyl and—C(NH)—NH₂, X¹, X², X³, X⁴, and X⁵ is, independently for each occurrencethereof, selected from the group consisting of H, F, Cl, Br, I,(C₁₋₁₀)alkyl, substituted (C₁₋₁₀)alkyl, aryl, substituted aryl, OH, NH₂,NO₂ and CN; and n is, independently for each occurrence thereof, 1, 2,3, 4 or 5; provided that: (I). when R2 is (C₁-C₃₀)acyl,aryl(C₁-C₃₀)acyl, substituted (C₂-C₃₀)acyl, or substitutedaryl(C₁-C₃₀)acyl, R³ is H, (C₁-C₃₀)alkyl, (C₁-C₃₀)heteroalkyl,(C₂-C₃₀)alkenyl, aryl(C₁-C₃₀)alkyl, substituted (C₁-C₃₀)alkyl,substituted (C₁-C₃₀)heteroalkyl, substituted (C₂-C₃₀)alkenyl orsubstituted aryl(C₁-C₃₀)alkyl; (II). when R12 is (C₁-C₄₀)acyl,(C₁-C₃₀)alkylsulfonyl, biotinyl or —C(NH)—NH₂, then R¹³ is H or(C₁-C₄₀)alkyl; (III). at least one of A¹⁵, A¹⁶, A¹⁷, A¹⁸, A¹⁹ or A²⁰must be selected from the group consisting of Ser(C(O)—R⁴),Thr(C(O)—R⁵), Glu(O—R⁶), Glu(NH—R⁷), Asp(O—R⁸), Asp(NH₂5 R⁹),Dap(S(O)₂—R¹⁰), Dab(S(O)₂—R¹¹), HN—CH((CH₂)_(n)—N(R¹²R¹³))—C(O),Cys(S—R¹⁴) Cys(R¹⁵), hCys(S—R¹⁶) and hCys(R¹⁷); and (IV). when any ofthe group consisting of A¹⁵, A¹⁶, A¹⁷, A¹⁹ and A²⁰ isHNCH((CH₂)_(n)—N(R¹²R¹³))—C(O), then R¹² must be biotinylated; or apharmaceutically acceptable salt thereof. 15-18. (canceled)
 19. A methodof claim 1, wherein said patient is a human.
 20. A method of claim 1,wherein said patient in need of gastrointestinal stimulation isexperiencing gastroesophageal reflux disease, ileus, emesis,gastroparesis, IBS, constipation, or colonic pseudo-obstruction.
 21. Amethod according to claim 20, wherein said patient is experiencingileus, emesis or gastroparesis. 22-27. (canceled)
 28. A method accordingto claim 21, wherein said patient is experiencing emesis.
 29. A methodaccording to claim 28, wherein said patient is experiencing emesisassociated with treatment with an anti-cancer chemotherapeutic agent,pregnancy, bulimia, or anorexia.
 30. A method according to claim 29,wherein said emesis is associated with treatment with an anti-cancerchemotherapeutic agent. 31-33. (canceled)
 34. A method according toclaim 21, wherein said patient is experiencing gastroparesis.
 35. Amethod according to claim 34, wherein said gastroparesis is associatedwith diabetes. 36-37. (canceled)